Apoptosis signal-regulating kinase inhibitors

ABSTRACT

The present invention relates to compounds of Formula (I): 
                         
wherein X 1 , X 2 , X 3 , X 4 , X 5 , X 6 , X 7 , X 8 , R 1 , R 2 , R 3  are defined above. The compounds have apoptosis signal-regulating kinase (“ASK1”) inhibitory activity, and are thus useful in the treatment of ASK1-mediated conditions, including autoimmune disorders, inflammatory diseases, cardiovascular diseases and neurodegenerative diseases. The invention also relates to pharmaceutical compositions comprising one or more of the compounds of Formula (I), and to methods of preparing the compounds of Formula (I).

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional application of U.S. patent applicationU.S. Ser. No. 12/834,673 filed Jul. 12, 2010, now pending, which claimsthe benefit under 35 U.S.C. 119(E) of U.S. Provisional PatentApplications Ser. No. 61/225,076 and 61/225,079, both filed Jul. 13,2009, and U.S. Provisional Patent Application Ser. No. 61/289,263, filedDec. 22, 2009, the entireties of each of which is herein incorporated byreference.

FIELD OF THE INVENTION

The present invention relates to novel compounds having enzymeinhibitory activity, and to their use in the treatment of ASK1-mediatedconditions, including autoimmune disorders, inflammatory diseases,including chronic kidney disease, cardiovascular diseases andneurodegenerative diseases. The invention also relates to methods fortheir preparation, and to pharmaceutical compositions containing suchcompounds.

BACKGROUND

Mitogen-activated protein kinase (MAPK) signaling cascades couplediverse extracellular and intracellular queues to appropriate cellularstress responses, including cell growth, differentiation, inflammation,and apoptosis (Kumar, S., Boehm, J., and Lee., J. C. (2003) Nat. Rev.Drug Dis. 2:717-726; Pimienta, G., and Pascual, J. (2007) Cell Cycle, 6:2826-2632). MAPKs exist in three groups, MAP3Ks, MAP2Ks, and MAPKs,which are sequentially activated. MAPK3s directly respond toenvironmental signals and phosphorylate MAP2Ks, which in turnphosphorylate specific MAPKs. MAPKs then mediated the appropriatecellular response by phosphorylating cellular substrates, includingtranscription factors that regulate gene expression.

Apoptosis signal-regulating kinase 1 (ASK1) is a member of themitogen-activated protein kinase kinase kinase (“MAP3K”) family thatactivates the c-Jun N-terminal protein kinase (“JNK.”) and p38 MAPkinase (Ichijo, H., Nishida, E, Irie, K., Dijke, P. T., Saitoh, M.,Moriguchi, T., Matsumoto, K., Miyazono, K., and Gotoh, Y. (1997)Science, 275, 90-94). ASK1 is activated by a variety of stimuliincluding oxidative stress, reactive oxygen species (ROS), LPS, TNF-α,FasL, ER stress, and increased intracellular calcium concentrations(Hattori, K., Naguro, I., Runchel, C., and Ichijo, H. (2009) Cell Comm.Signal. 7:1-10; Takeda, K., Noguchi, T., Naguro, I., and Ichijo, H.(2007) Annu. Rev. Pharmacol. Toxicol. 48: 1-8.27; Nagai, H., Noguchi,T., Takeda, K., and Ichijo, I. (2007) J. Biochem. Mol. Biol. 40:1-6).ASK1 undergoes activation via autophosphorylation at Thr838 in responseto these signals and in turn phosphorylates MAP2Ks, such as MKK3/6 andMKK4/7, which then phosphorylate and activate p38 and JNK MAPKs,respectively. ASK2 is a related MAP3K that shares 45% sequence homologywith ASK1 (Wang, X. S., Diener, K., Tan, T-H., and Yao, Z. (1998)Biochem. Biophys. Res. Commun. 253, 33-37. Although ASK2 tissuedistribution is restricted, in some cell types ASK1 and ASK2 have beenreported to interact and function together in a protein complex (Takeda,K., Shimozono, R., Noguchi, T., Umeda, T., Morimoto, Y., Naguro, I.,Tobiume, K., Saitoh, M., Matsuzawa, A., and Ichijo, H. (2007) J. Biol.Chem. 282: 7522-7531; Iriyarna, T., et al. (2009) Embo J. 28: 843-853)In non stressed conditions, A SK1 is kept in an inactive state throughbinding to its repressor Thioredoxin (Trx) (Saitoh, M., Nishitoh, H.,Fuji, M., Takeda, K., Tobiume, K., Sawada, Y., Kawabata, M., Miyazono,K., and Ichijo, H. (1998) Embo J. 17:2596-2606), and through associationwith AKT (Zhang, L., Chen, J. and Fu, H. (1999) Proc. Natl. Acad. Sci.U.S.A 96:8511-8515).

Phosphorylation of ASK1 protein can lead to apoptosis or other cellularresponses depending on the cell type. ASK1 activation and signaling havebeen reported to play an important role in a broad range of diseasesincluding neurodegenerative, cardiovascular, inflammatory, autoimmunity,and metabolic disorders. In addition, ASK1 has been implicated inmediating organ damage following ischemia and reperfusion of the heart,brain, and kidney (Watanabe et al. (2005) BBRC 333, 562-567; Zhang etal., (2003) Life Sci 74-37-43; Terada et al. (2007) BBRC 364: 1043-49).Emerging evidence suggests that ASK2, either alone or in a complex withASK1, may play important roles in human diseases as well. Therefore,therapeutic agents that function as inhibitors of ASK1 and ASK2signaling complexes have the potential to remedy or improve the lives ofpatients suffering from such conditions.

U.S. Publication No. 2007/0276050 describes methods for identifying ASK1inhibitors useful for preventing and/or treating cardiovascular diseaseand methods for preventing and/or treating cardiovascular disease in ananimal. The methods comprise administering to the animal an ASK1inhibitor and, optionally, a hypertensive compound.

U.S. Publication No. 2007/0167386 reports a drug for at least one ofprevention and treatment of cardiac failure containing a compound thatinhibits a functional expression of ASK1 protein in a cardiomyocyte, anda method for screening the drug.

WO2009027283 discloses triazolopyridine compounds, methods forpreparation thereof and methods for treating autoimmune disorders,inflammatory diseases, cardiovascular diseases and neurodegenerativediseases.

SUMMARY OF THE INVENTION

Accordingly, the present invention provides novel compounds thatfunction as ASK1 inhibitors. In a first aspect, the invention relates tocompounds of Formula I:

wherein:

-   R¹ is alkyl, alkenyl, alkynyl, cycloalkyl, aryl, heteroaryl, or    heterocyclyl, all of which are optionally substituted with 1, 2, or    3 substituents selected from halo, oxo, alkyl, cycloalkyl,    heterocyclyl, aryl, aryloxy, —NO₂, R⁶, —C(O)—R⁶,    —OC(O)—R⁶—C(O)—O—R⁶, —C(O)—N(R⁶)(R⁷), —OC(O)—N(R⁶)(R⁷), —S—R⁶,    —S(═O)—R⁶, —S(═O)₂R⁶, —S(═O)₂—N(R⁶)(R⁷), —S(═O)₂—O—R⁶, —N(R⁶)(R⁷),    —N(R⁶)—C(O)—R⁷, —N(R⁶)—C(O)—O—R⁷, —N(R⁶)—C(O)—N(R⁶)(R⁷),    —N(R⁶)—S(═O)₂—R⁶, —CN, and —O—R⁶,-   wherein alkyl, cycloalkyl, heterocyclyl, phenyl, and phenoxy are    optionally substituted by 1, 2, or 3 substituents selected from    alkyl, cycloalkyl, alkoxy, hydroxyl, and halo;-   wherein R⁶ and R⁷ are independently selected from the group    consisting of hydrogen, C₁-C₁₅ alkyl, cycloalkyl, heterocyclyl,    aryl, and heteroaryl, all of which are optionally substituted with    1-3 substituents selected from halo, alkyl, mono- or dialkylamino,    alkyl or aryl or heteroaryl amide, —CN, lower alkoxy, —CF₃, aryl,    and heteroaryl; or    -   R⁶ and R⁷ when taken together with the nitrogen to which they        are attached form a heterocycle;-   R² is hydrogen, halo, cyano, alkoxy, or alkyl optionally substituted    by halo;-   R³ is aryl, heteroaryl, or heterocyclyl, all of which are optionally    substituted with one or more substituents selected from alkyl,    alkoxy, cycloalkyl, cycloalkylalkyl, aryl, arylalkyl, heteroaryl,    heteroarylalkyl, heterocyclyl, heterocyclylalkyl, halo, oxo, —NO₂,    haloalkyl, haloalkoxy, —CN, —O—R⁶, —O—C(O)—R⁶, —O—C(O)—N(R⁶)(R⁷),    —S—R⁶, —N(R⁶)(R⁷), —S(═O)—R⁶, —S(═O)₂R⁶, —S(═O)₂—N(R⁶)(R⁷),    S(═O)₂—O—R⁶, —N(R⁶)—C(O)—R⁷, —N(R⁶)—C(O)—O—R⁷,    —N(R⁶)—C(O)—N(R⁶)(R⁷), —C(O)—R⁶, —C(O)—O—R⁶, —C(O)—N(R⁶)(R⁷), and    —N(R⁶)—S(═O)₂—R⁷, wherein the alkyl, alkoxy, cycloalkyl, aryl,    heteroaryl or heterocyclyl is further optionally substituted with    one or more substituents selected from halo, oxo, —NO₂, alkyl,    haloalkyl, haloalkoxy,    -   —N(R⁶)(R⁷), —C(O)—R⁶, —C(O)—O—R⁶, —C(O)—N(R⁶)(R⁷), —CN, —O—R⁶,        cycloalkyl, aryl, heteroaryl and heterocyclyl;        with the proviso that the heteroaryl or heterocyclyl moiety        includes at least one ring nitrogen atom;-   X¹, X², X³, X⁴, X⁵, X⁶, X⁷ and X⁸ are independently C(R⁴) or N, in    which each R⁴ is independently hydrogen, alkyl, alkoxy, cycloalkyl,    aryl, heteroaryl, heterocyclyl, halo, —NO₂, haloalkyl, haloalkoxy,    —CN, —O—R⁶, —S—R⁶, —N(R⁶)(R⁷), —S(═O)—R⁶, —S(═O)₂R⁶,    —S(═O)₂—N(R⁶)(R⁷), —S(═O)₂—O—R⁶, —N(R⁶)—C(O)—R⁶, —N(R⁶)—C(O)—O—R⁷,    —N(R⁶)—C(O)—N(R⁶)(R⁷), —C(O)—R⁶, —C(O)—O—R⁶, —C(O)—N(R⁶)(R⁷), or    —N(R⁶)—S(═O)₂—R⁷, wherein the alkyl, cycloalkyl, aryl, heteroaryl,    and heterocyclyl is further optionally substituted with one or more    substituents selected from halo, oxo, —NO₂, —CF₃, —O—CF₃,    —N(R⁶)(R⁷), —C(O)—R⁶, —C(O)—O—R⁷, —C(O)—N(R⁶)(R⁷), —CN, —O—R⁶; or-   X⁵ and X⁶ or X⁶ and X⁷ are joined to provide optionally substituted    fused aryl or optionally substituted fused heteroaryl; and-   with the proviso that at least one of X², X³, and X⁴ is C(R⁴);-   at least two of X⁵, X⁶, X⁷, and X⁸ are C(R⁴); and-   at least one of X², X³, X⁴, X⁵, X⁶, X⁷ and X⁸ is N.

In a second aspect, the invention relates to a method of using thecompounds of Formula (I) in the treatment of a disease or condition in amammal that is amenable to treatment by an ASK1 inhibitor. Such diseasesinclude autoimmune disorders, inflammatory diseases, cardiovasculardiseases and neurodegenerative diseases.

In a third aspect, the invention relates to pharmaceutical formulationscomprising a therapeutically effective amount of a compound of theinvention and at least one pharmaceutically acceptable excipient.

In a fourth aspect, the invention relates to methods of preparing thecompounds of Formula (I).

Non-limiting examples of R³ are shown below:

in which:

-   R¹¹ is hydrogen, alkyl, or cycloalkyl, wherein alkyl and cycloalkyl    are optionally substituted by hydroxyl or halo;-   R¹² is hydrogen, alkyl, cycloalkyl, —S(═O)—R⁶ or —S(═O)₂R⁶, wherein    alkyl and cycloalkyl are optionally substituted by hydroxyl or halo.

One embodiment of the invention includes those compounds of Formula (I)in which X¹, X², and X⁵ are all N, and X³, X⁴, X⁶, X⁷, and X⁸ are C(R⁴).This group includes compounds in which R¹ is optionally substitutedalkyl, optionally substituted cycloalkyl, or optionally substitutedheterocyclyl, particularly where the optional substitutions are 1, 2, or3 substituents chosen from hydroxyl, halo, or cycloalkyl. Within thisgroup, a subgroup includes compounds in which R³ is optionallysubstituted aryl, optionally substituted heteroaryl or optionallysubstituted heterocyclyl, wherein the heteroaryl or heterocyclylmoieties contain 1, 2 or 3 ring nitrogen atoms, and the aryl,heteroaryl, and heterocyclyl moieties are optionally substituted byalkyl, cycloalkyl, halo, cyano,—or OR⁶, in which alkyl and cycloalkylare optionally substituted by hydroxyl or halo. A preferred group of R³moieties includes those non-limiting examples described above.

Another embodiment of the invention includes those compounds of Formula(I) in which X¹ and X⁵ are N, and X², X³, X⁴, X⁶, X⁷, and X⁸ are C(R⁴).This group includes compounds in which R¹ is optionally substitutedalkyl, optionally substituted cycloalkyl, or optionally substitutedheterocyclyl., particularly where the optional substitutions are 1, 2,or 3 substituents chosen from hydroxyl, halo, or cycloalkyl. Within thisgroup, a subgroup includes compounds in which R³ is optionallysubstituted aryl, optionally substituted heteroaryl or optionallysubstituted heterocyclyl, wherein the heteroaryl or heterocyclylmoieties contain 1, 2 or 3 ring nitrogen atoms, and the aryl,heteroaryl, and heterocyclyl moieties are optionally substituted byalkyl, cycloalkyl, halo, cyano,—or OR⁶, in which alkyl and cycloalkylare optionally substituted by hydroxyl or halo. A preferred group of R³moieties includes: those non-limiting examples described above.

Another embodiment of the invention includes those compounds of Formula(I) in which X¹ and X² are N, and X³, X⁴, X⁵, X⁶, X⁷, and X⁸ are C(R⁴).This group includes compounds in which R¹ is optionally substitutedalkyl, optionally substituted cycloalkyl, or optionally substitutedheterocyclyl., particularly where the optional substitutions are 1, 2,or 3 substituents chosen from hydroxyl, halo, or cycloalkyl. Within thisgroup, a subgroup includes compounds in which R³ is optionallysubstituted aryl, optionally substituted heteroaryl or optionallysubstituted heterocyclyl, wherein the heteroaryl or heterocyclylmoieties contain 1, 2 or 3 ring nitrogen atoms, and the aryl,heteroaryl, and heterocyclyl moieties are optionally substituted byalkyl, cycloalkyl, halo, cyano,—or OR⁶, in which alkyl and cycloalkylare optionally substituted by hydroxyl or halo. A preferred group of R³moieties includes: those non-limiting examples described above.

Another embodiment of the invention includes those compounds of Formula(I) in which X¹ is C(R⁴). This group includes compounds in which R¹ isoptionally substituted alkyl, optionally substituted cycloalkyl, oroptionally substituted heterocyclyl., particularly where the optionalsubstitutions are 1, 2, or 3 substituents chosen from hydroxyl, halo, orcycloalkyl. Within this group, a subgroup includes compounds in which R³is optionally substituted aryl, optionally substituted heteroaryl oroptionally substituted heterocyclyl, wherein the heteroaryl orheterocyclyl moieties contain 1, 2 or 3 ring nitrogen atoms, and thearyl, heteroaryl, and heterocyclyl moieties are optionally substitutedby alkyl, cycloalkyl, halo, cyano,—or OR⁶, in which alkyl and cycloalkylare optionally substituted by hydroxyl or halo. A preferred group of R³moieties includes: those non-limiting examples described above.

The compounds of the invention include, but are not limited to, thosecompounds named below:

-   5-(2,5-difluorophenyl)-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)nicotinamide;-   4-(imidazo[1,2-a]pyridin-3-yl)-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-picolinamide;-   4-(2-aminopyrimidin-5-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-thiazol-3-yl)phenyl)picolinamide;-   N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-5-phenylnicotinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-phenylpicolinamide;-   N-(3-(4-(tetrahydro-2H-pyran-4-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine    2′-carboxamide;-   2-hydroxy-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-6-phenylpyrimidine-4-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1H-imidazol-1-yl)picolinamide;-   N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-4-phenylpicolinamide-   N-(3-(4-(3-amino-3-oxopropyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1H-1,2,4-triazol-1-yl)picolinamide;-   N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-6-phenylpicolinamide;-   N-(3-(4-(2-acetamidoethyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-methylpiperazin-1-yl)picolinamide;-   N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-2,3′-bipyridine-6-carboxamide;-   N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-4-morpholinopicolinamide;-   N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(quinolin-6-yl)picolinamide;-   (R)—N-(3-(4-(1-hydroxypropan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-hydroxy-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-3,3′-bipyridine-5-carboxamide;-   (S)—N-(3-(4-(1-hydroxypropan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(3-oxopiperazin-1-yl)picolinamide;-   N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-methoxy-3,4′-bipyridine-2′-carboxamide;-   4-(3-aminopyrrolidin-1-yl)-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-2-phenylisonicotinamide;-   6-amino-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   (R)—N-(3-(4-(2-hydroxypropyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   5-methoxy-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   methyl    2′-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenylcarbamoyl)-3,4′-bipyridin-6-ylcarbamate;-   5-methoxy-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   methyl    2′-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenylcarbamoyl)-3,4′-bipyridin-6-yl    carbamate;-   (S)—N-(3-(4-(2-hydroxypropyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   4-(1-methyl-1H-imidazol-5-yl)-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1-methyl-1H-imidazol-5-yl)picolinamide;-   4-(1H-benzo[d]imidazol-1-A-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(2,4-dimethoxypyrimidin-5-yl)picolinamide;-   N-(3-(4-((1-hydroxycyclopropyl)methyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-phenyl-1H-imidazol-1-yl)picolinamide;-   6-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   (S)—N-(3-(4-(2-hydroxypropyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclobutyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N2′-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′,6-dicarboxamide;-   (S)—N-(3-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopentyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(trifluoromethyl)-3,4′-bipyridine-2′-carboxamide;-   N2′-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′,5-dicarboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(2-methyl-1H-imidazol-1-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-methyl-3,4′-bipyridine-2′-carboxamide;-   5-cyano-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-methyl-1H-imidazol-1-yl)picolinamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide;-   2-amino-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4,5-dimethyl-1H-imidazol-1-yl)picolinamide;-   N-(3-(4-((1S,2S)-2-methylcyclopropyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4)-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-2-methoxy-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(trifluoromethyl)-1H-imidazol-1-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(2,2,2-trifluoroethoxy)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1-methyl-1H-pyrazol-4-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(2-methoxypyrimidin-5-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-methyl-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(imidazo[1,2-a]pyridin-3-yl)picolinamide;-   ethyl-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-(2,2,2-trifluoroethyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   6-chloro-[3,2′,5′,4″]terpyridine-2″-carboxylic    acid[3-(4-cyclopropyl-4H-[1,2,4]triazol-3-yl)-phenyl]amide-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(pyrrolidin-1-yl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5-(trifluoromethyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(1-cyclopropyl-1H-imidazol-5-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1,2-dimethyl-1H-imidazol-5-yl)picolinamide;-   4-(1H-benzo[d][1,2,3]triazol-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-sulfamoylphenyl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5-methoxy-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3)phenyl)-6-fluoro-5-methyl-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5-fluoro-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-2-methyl-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-1-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(N-methylsulfamoyl)phenyl)picolinamide;-   N5-tert-butyl-N2′-(3    (4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′,5-dicarboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(pyrazin-2-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(N-isopropylsulfamoyl)phenyl)picolinamide;-   chloro-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   4-(1H-benzo[d]imidazol-1-yl)-N-(3-(1-cyclopropyl-1H-imidazol-5-yl)phenyl)picolinamide;-   6-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(3-(methylsulfonyl)phenyl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(isoquinolin-4-yl)picolinamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4-(methylsulfonyl)phenyl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(2-(methylsulfonyl)phenyl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1,5-dimethyl-1H-pyrazol-4-yl)picolinamide;-   6-cyclobutyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-isopropyl-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-5H-1,2,4-triazol-3-yl)phenyl)-4-(4-(methylsulfonyl)phenyl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(dimethylamino)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(pyridin-3-yl)quinoline-2-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1H-pyrrolo[2,3-b]pyridin-5-yl)picolinamide;-   6-cyclopropoxy-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1H-imidazo[4,5-b]pyridin-1-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-fluoro-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(2-oxoimidazolidin-1-yl)phenyl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(3H-imidazo[4,    5-1)]pyridin-3-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-isopropoxy-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-ethyl-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1H-imidazo[4,5-c]pyridin-1-yl)picolinamide;-   6-cyclobutoxy-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   6-cyclopropyl-N-(3-(1-cyclopropyl-1H-imidazol-5-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(quinolin-3-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(N-cyclopropylsulfamoyl)    phenyl)picolinamide;-   N-(3-(1-cyclopropyl-1H-imidazol-5-yl)phenyl)-4-(quinolin-3-yl)picolinamide;-   6-cyclopentyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(imidazo[2,1-b][1,3,4]thiadiazol-5-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(5-cyclopropylpyrazin-2-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(1-methyl-2-oxopyrrolidin-3-yl)-3,4′-bipyridine-2′-carboxamide;-   4-(4-chloro-1H-imidazol-1-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   6-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5-fluoro-3,4′-bipyridine-2′-carboxamide;-   (S)-4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(3-methylbutan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   6′-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-2,3′-bipyridine-6-carboxamide;-   6′-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-2,3′-bipyridine-4-carboxamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-(6-cyclopropylpyridin-3-yl)-2,4-difluorobenzamide;-   6′-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2,3′-bipyridine-4-carboxamide;-   6′-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,3′-bipyridine-5-carboxamide;-   6′-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2,3′-bipyridine-6-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(5-methyl-4-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-1-yl)picolinamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(5-methyl-4-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-1-yl)picolinamide;-   4-(5-cyclopropyl-4-methyl-4H-1,2,4-triazol-3-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   4-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(3-methyl-1,2,4-oxadiazol-5-yl)picolinamide;-   6-cyclopropyl-N-(3-(4-(3-hydroxybutan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   4-chloro-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-(6-cyclopropylpyridin-3-yl)-2-fluorobenzamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(5-(1-hydroxyethyl)-1,3,4-oxadiazol-2-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(6-methoxyquinolin-3-yl)picolinamide;-   6-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5′-methyl-3,4′-bipyridine-2′-carboxamide;-   6-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6′-methyl-3,4′-bipyridine-2′-carboxamide;-   6-cyclopropyl-N-(6-(4-((2R)-3-hydroxybutan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide;-   6-cyclopropyl-N-(6-(4-((2S,3R)-3-hydroxybutan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide;-   6-cyclopropyl-N-(6-(4-((2S,3S)-3-hydroxybutan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide;-   6-cyclopropyl-N-(6-(4-(1-(pyrrolidin-1-yl)propan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-b]pyridin-6-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(isopropyl-1-pyrrolo[3,2-b]pyridin-6-yl)picolinamide;-   (S)-6-cyclopropyl-N-(3-(4-(3,3-dimethylbutan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   6-cyclopropyl-N-(6-(4-(1-methylpiperidin-4-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-sec-butyl-4H-1,2,4-triazol-3-yl)phenyl)-6-cyclopropyl-3,4′-bipyridine-2′-carboxamide;-   (S)-6-cyclopropyl-N-(3-(4-(1-cyclopropylethyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   6-cyclopropyl-N-(3-(4-(pentan-3-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   (S)-6-cyclopropyl-N-(3-(4-(1-methoxypropan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   6-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-6′-methyl-3,4′-bipyridine-2′-carboxamide;-   (S)-6-cyclopropyl-N-(6-(4-(1-methoxypropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-dine-2′-carboxamide;-   (S)—N-(3-(4-sec-butyl-4H-1,2,4-triazol-3-yl)phenyl)-6-cyclopropyl-3,4′-bipyridine-2′-carboxamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(2,2,2-trifluoro-1-methoxyethyl)-1H-imidazol-1-yl)benzamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(6-cyclopropylpyridin-3-yl)-7,8-dimethyl    quinoline-2-carboxamide;-   (S)-6-cyclopropyl-N-(3-(4-(3-methylbutan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   (R)-6-cyclopropyl-N-(3-(4-(1-(2,6-dimethylphenoxy)propan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(6-cyclopropylpyridin-3-yl)-7,8-dimethylquinoline-2-carboxamide;-   3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-methoxybenzamide;-   4-chloro-3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;-   4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)quinoline-2-carboxamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(6-cyclopropylpyridin-3-yl)quinoline-2-carboxamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-(6-cyclopropylpyridin-3-yl)-2-fluorobenzamide;-   (S)-6-cyclopropyl-N-(3-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   (S)-tert-butyl    2-(3-(3-(6-cyclopropyl-3,4′-bipyridine-2′-carboxamido)phenyl)-4H-1,2,4-triazol-4-yl)propanoate;-   N-(3-(4-cyclobutyl-4H-1,2,4-triazol-3-yl)phenyl)-6-cyclopropyl-3,4′-bipyridine-2′-carboxamide;-   (S)-6-cyclopropyl-N-(3-(4-(1-phenylethyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   6-cyclopropyl-N-(3-(4-isopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;-   (S)-3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-(1-phenylethyl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;-   N-(6-(1-cyclopropyl-1H-imidazol-5-yl)pyridin-2-yl)-4-(4,5-dimethyl-1H-imidazol-1-yl)picolinamide;-   N-(6-(1-cyclopropyl-1H-imidazol-5-yl)pyridin-2-yl)-6-(2-hydroxypropan-2-yl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-(cyclopropylmethyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridin    carboxamide;-   4-(4-cyclopropyl-2-methyl-1H-imidazol-1-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   4-(4-cyclopropyl-2-methyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)picolinamide;-   4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-isopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(cyclopropylmethyl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   4-(4-cyclopropyl-1-imidazol-1-yl)-N-(3-(4-(1-phenyl    ethyl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-1-yl)picolinamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4-(trifluoromethyl)-1H-imidazol-1-yl)picolinamide;-   (R)-4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1,5-naphthyridin-3-yl)picolinamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(1,5-naphthyridin-3-yl)benzamide;-   3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-isopropyl-1H-imidazol-1-yl)benzamide;-   3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-methylbenzamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-1-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-1-yl)picolinamide;-   5-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-methylbenzamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(perfluoroethyl)-1H-imidazol-1-yl)picolinamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4-(perfluoroethyl)-1H-imidazol-1-yl)picolinamide;-   3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-methylbenzamide;-   4-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)picolinamide;-   4-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   4-(5-cyclopropyl-1H-1,2,4-triazol-1-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   N-(6-(4-cyclopropyl-4-H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)benzamide;-   3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-fluorobenzamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4-(2,2,2-trifluoro-1-hydroxyethyl)-1H-imidazol-1-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(2,2,2-trifluoro-1-hydroxyethyl)-1H-imidazol-1-yl)picolinamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(2,2,2-trifluoro-1-hydroxyethyl)-1H-imidazol-1-yl)benzamide;-   3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-methylbenzamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4,5-dimethyl-1H-imidazol-1-yl)benzamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4,5,6,7-tetrahydro-1-benzo[d]imidazol-1-yl)benzamide;-   1-(3-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-ylcarbamoyl)phenyl)-5-methyl-1H-imidazole-4-carboxylic    acid;-   (S)-3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-(1-phenylethyl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;-   6-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5′-methyl-3,4′-bipyridine-2′-carboxamide;-   (S)-3-(4,5-dimethyl-1H-imidazol-1-yl)-N-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(2-ethylpyrimidin-5-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5-ethyl-3,4′-bipyridine-2′-carboxamide;-   6-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)-4-fluorophenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)-4-fluorophenyl)-6-ethyl-3,4′-bipyridin    carboxamide;-   6-tert-butyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(quinolin-3-yl)benzamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(6-cyclopropylpyridin-3-yl)benzamide;-   6-cyclopropyl-N-(2-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-4-yl)-3,4′-bipyridine-2′-carboxamide;-   N-(2-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-4-yl)-4-(quinolin-3-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)picolinamide;-   6-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)-2-fluorophenyl)-3,4′-bipyridine-2′-carboxamide;-   5-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)-2-fluorophenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-ethyl-1H-imidazol-1-yl)picolinamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4-methyl-1H-imidazol-1-yl)picolinamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4,5-dimethyl-1H-imidazol-1-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(6-(2,2,2-trifluoroethyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-isopropyl-1H-imidazol-1-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(2-hydroxypropan-2-yl)-3,4′-bipyridine-2′-carboxamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-6-(2-hydroxypropan-2-yl)-3,4′-bipyridine-2′-carboxamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazole-3-yl)pyridin-2-yl)-4-(4-isopropyl-1H-imidazol-1-yl)picolinamide;-   6-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)-5-fluorophenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)-5-fluorophenyl)-3,4′-bipyridine-2′-carboxamide;-   4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(2,2,2-trifluoroethyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(6-isopropyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(6-methyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(3-hydroxypiperidin-1-yl)picolinamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(3-hydroxypiperidin-1-yl)picolinamide;-   6-cyclopropyl-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-ethyl-3-oxopiperazin-1-yl)picolinamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4-ethyl-3-oxopiperazin-1-yl)picolinamide;-   (R)-6-cyclopropyl-N-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-isopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   6-cyclopentyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(1-methyl-2-oxopyrrolidin-3-yl)-3,4′-bipyridine-2′-carboxamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4-(N-methyl    sulfamoyl)phenyl)picolinamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(quinolin-3-yl)picolinamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4-phenyl-1H-imidazol-1-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-propyl-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-neopentyl-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1-methyl-2-phenyl-1H-imidazol-5-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(ethylsulfonyl)phenyl)-picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(isopropylsulfonyl)phenyl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(ethylamino)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(cyclopropylamino)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(imidazo[2,1-b][1,3,4]thiadiazol-5-yl)picolinamide;-   4-(4-chloro-1H-imidazol-1-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(2-cyclopropylpyrimidin-5-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6′-(trifluoromethyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(quinolin-3-yl)-6-(trifluoromethyl)picolinamide;-   N-(6-(1-cyclopropyl-1H-imidazol-5-yl)pyridin-2-yl)-4-(quinolin-3-yl)picolinamide;-   6-cyclopropyl-N-(6-(1-cyclopropyl-1H-imidazol-5-yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1H-pyrrolo[3,2-b]pyridin-6-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-cyclopropylphenyl)picolinamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(pyridin-3-yl)benzamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(methylthio)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(isobutylthio)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(5-cyclopropylpyrazin-2-yl)picolinamide;-   6-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5-fluoro-3,4′-bipyridine-2′-carboxamide;-   5-chloro-6-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(2-methoxyethylamino)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(methylsulfonyl)piperazin-1-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-ethyl-5-fluoro-3,4′-bipyridine-2′-carboxamide;-   5-chloro-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-ethyl-3,4′-bipyridine-2′-carboxamide;-   4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5,6-diethyl-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(furo[3,2-b]pyridin-6-yl)picolinamide;-   N-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(3-methyl-3H-imidazo[4,5-b]pyridin-6-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(6-cyclopropylpyridin-3-yl)pyrimidine-4-carboxamide.-   6-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6′-methyl-3,4′-bipyridine-2′-carboxamide;-   6-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5′-methyl-3,4′-bipyridine-2′-carboxamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(5-methyl-4-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-1-yl)picolinamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(5-methyl-4-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-1-yl)picolinamide;-   6′-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2,3′-bipyridine-6-carboxamide;-   6′-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,3′-bipyridine-5-carboxamide;-   6′-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2,3′-bipyridine-4-carboxamide;-   N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-(6-cyclopropylpyridin-3-yl)-2,4-difluorobenzamide;-   6′-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-2,3′-bipyridine-6-carboxamide;-   (S)-4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(3-methylbutan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   4-chloro-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-(6-cyclopropylpyridin-3-yl)-2-fluorobenzamide;-   6-cyclopropyl-N-(3-(4-(2-phenylcyclopropyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(cyclopropylmethyl)-3,4′-bipyridine-2′-carboxamide;-   3-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;-   4-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   6-cyclopropyl-N-(3-(4-phenyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   6-cyclopropyl-N-(3-(4-(pyridin-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   6-cyclopropyl-N-(3-(4-(pyridin-3-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   6-cyclopropyl-N-(3-(4-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   6-cyclopropyl-N-(3-(4-(pyrimidin-5-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   N-(3-(4-(but-2-ynyl)-4H-1,2,4-triazol-3-yl)phenyl)-6-cyclopropyl-3,4′-bipyridine-2′-carboxamide;-   6-cyclopropyl-N-(3-(4-(1-(pyridin-3-yloxy)propan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   6-cyclopropyl-N-(3-(4-(1-(2,2,2-trifluoroethoxy)propan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;-   4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-phenyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide-   4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(pyridin-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(pyridin-3-yl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(pyrimidin-5-yl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamide;-   N-(3-(4-(but-2-ynyl)-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-cyclopropyl-1H-imidazol-1-yl)picolinamide;-   4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(1-(pyridin-3-yloxy)propan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamide    and-   4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(1-(2,2,2-trifluoroethoxy)propan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamide.

DETAILED DESCRIPTION OF THE INVENTION

Definitions and General Parameters

As used in the present specification, the following words and phrasesare generally intended to have the meanings as set forth below, exceptto the extent that the context in which they are used indicatesotherwise.

The term “alkyl” refers to a monoradical branched or unbranchedsaturated hydrocarbon chain having from 1 to 20 carbon atoms. This termis exemplified by groups such as methyl, ethyl, n-propyl, iso-propyl,n-butyl, iso-butyl, t-butyl, n-hexyl, n-decyl, tetradecyl, and the like.

The term “substituted alkyl” refers to:

1) an alkyl group as defined above, having 1, 2, 3, 4 or 5 substituents,(typically 1, 2, or 3 substituents) selected from the group consistingof alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino,acyloxy, amino, aminocarbonyl, alkoxycarbonylamino, azido, cyano,halogen, hydroxy, keto, thiocarbonyl, carboxy, carboxyalkyl, arylthio,heteroarylthio, heterocyclylthio, thiol, alkyl thio, aryl, aryloxy,heteroaryl, aminosulfonyl, aminocarbonylamino, heteroaryloxy,heterocyclyl heterocyclooxy, hydroxyamino, alkoxyamino, nitro,—SO-alkyl, —SO-aryl, —SO-heteroaryl, —SO₂-alkyl, SO₂-aryl and—SO₂-heteroaryl. Unless otherwise constrained by the definition, allsubstituents may optionally be further substituted by 1, 2, or 3substituents chosen from alkyl, carboxy, carboxyalkyl, aminocarbonyl,hydroxy, alkoxy, halogen, CF), amino, substituted amino, cyano, and—S(O)_(n)R, where R is alkyl, aryl, or heteroaryl and n is 0, 1 or 2; or

2) an alkyl group as defined above that is interrupted by 1-10 atoms(e.g. 1, 2, 3, 4, or 5 atoms) independently chosen from oxygen, sulfurand NRa—, where Ra is chosen from hydrogen, alkyl, cycloalkyl, alkenyl,cycloalkenyl, alkynyl, aryl, heteroaryl and heterocyclyl. Allsubstituents may be optionally further substituted by alkyl, alkoxy,halogen, CF₃, amino, substituted amino, cyano, or —S(O)_(n)R, in which Ris alkyl, aryl, or heteroaryl and n is 0, 1 or 2; or

3) an alkyl group as defined above that has both 1, 2, 3, 4 or 5substituents as defined above and is also interrupted by 1-10 atoms(e.g. 1, 2, 3, 4, or 5 atoms) as defined above.

The term “lower alkyl” refers to a monoradical branched or unbranchedsaturated hydrocarbon chain having 1, 2, 3, 4, 5, or 6 carbon atoms.This term is exemplified by groups such as methyl, ethyl, n-propyl,iso-propyl, n-butyl, iso-butyl, t-butyl, n-hexyl, and the like.

The term “substituted lower alkyl” refers to lower alkyl as definedabove having 1 to 5 substituents (typically 1, 2, or 3 substituents), asdefined for substituted alkyl, or a lower alkyl group as defined abovethat is interrupted by 1, 2, 3, 4, or 5 atoms as defined for substitutedalkyl, or a lower alkyl group as defined above that has both 1, 2, 3, 4or 5 substituents as defined above and is also interrupted by 1, 2, 3,4, or 5 atoms as defined above.

The term “alkylene” refers to a diradical of a branched or unbranchedsaturated hydrocarbon chain, typically having from 1 to 20 carbon atoms(e.g. 1-10 carbon atoms, or 1, 2, 3, 4, 5 or 6 carbon atoms). This termis exemplified by groups such as methylene (—CH₂—), ethylene (—CH₂CH₂—),the propylene isomers (e.g., —CH₂CH₂CH₂— and —CH(CH₃)CH₂—), and thelike.

The term “lower alkylene” refers to a diradical of a branched orunbranched saturated hydrocarbon chain, typically having 1, 2, 3, 4, 5,or 6 carbon atoms.

The term “substituted alkylene” refers to:

(1) an alkylene group as defined above having 1, 2, 3, 4, or 5substituents (typically 1, 2, or 3 substituents) selected from the groupconsisting of alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, cycloalkenyl,acyl, acylamino, acyloxy, amino, aminocarbonyl, alkoxycarbonylamino,azido, cyano, halogen, hydroxy, keto, thiocarbonyl, carboxy,carboxyalkyl, arylthio, heteroarylthio, heterocyclylthio, thiol,alkylthio, aryl, aryloxy, heteroaryl, aminosulfonyl, aminocarbonylamino,heteroaryloxy, heterocyclyl, heterocyclooxy, hydroxyamino, alkoxyamino,nitro, —SO-alkyl, —SO-aryl, —SO-heteroaryl, —SO₂-alkyl, SO₂-aryl and—SO₂-heteroaryl. Unless otherwise constrained by the definition, allsubstituents may optionally be further substituted by 1, 2, or 3substituents chosen from alkyl, carboxy, carboxyalkyl, aminocarbonyl,hydroxy, alkoxy, halogen, CF₃, amino, substituted amino, cyano, and—S(O)_(n)R, where R is alkyl, aryl, or heteroaryl and n is 0, 1 or 2; or

(2) an alkylene group as defined above that is interrupted by 1-10groups (e.g. 1, 2, 3, 4, or 5 groups) independently chosen from —O—,—S—, sulfonyl, —C(O)—, —C(O)O—, —C(O)N—, and —NRa—, where Ra is chosenfrom hydrogen, optionally substituted alkyl, cycloalkyl, cycloalkenyl,aryl, heteroaryl and heterocyclyl; or

(3) an alkylene group as defined above that has both 1, 2, 3, 4 or 5substituents as defined above and is also interrupted by 1-10 groups asdefined above. Examples of substituted alkylenes are chloromethylene(—CH(Cl)—), aminoethylene (—CH(NH₂)CH₂—), methylaminoethylene(—CH(NHMe)CH₂—), 2-carboxypropylene isomers (—CH₂CH(CO₂H)CH₂—),ethoxyethyl (—CH₂CH₂O—CH₂CH₂—), ethylmethylaminoethyl(—CH₂CH₂—N(CH₃)—CH₂CH₂—), 1-ethoxy-2-(2-ethoxy-ethoxy)ethane(—CH₂CH₂O—CH₂CH₂—OCH₂CH—OCH₂CH₂—), and the like.

The term “aralkyl” or “arylalkyl” refers to an aryl group covalentlylinked to an alkylene group, where aryl and alkylene are defined herein.“Optionally substituted aralkyl” refers to an optionally substitutedaryl group covalently linked to an optionally substituted alkylenegroup. Such aralkyl groups are exemplified by benzyl, phenylethyl,3-(4-methoxyphenyl)propyl, and the like.

The term “alkoxy” refers to the group R—O—, where R is optionallysubstituted alkyl or optionally substituted cycloalkyl, or R is a group—Y—Z, in which Y is optionally substituted alkylene and Z is optionallysubstituted alkenyl, optionally substituted alkynyl; or optionallysubstituted cycloalkenyl, where alkyl, alkenyl, alkynyl, cycloalkyl andcycloalkenyl are as defined herein. Typical alkoxy groups are alkyl-O—and include, by way of example, methoxy, ethoxy, n-propoxy, iso-propoxy,n-butoxy, tert-butoxy, sec-butoxy, n-pentoxy, n-hexyloxy,1,2-dimethylbutoxy, and the like.

The term “lower alkoxy” refers to the group R—O— in which R isoptionally substituted lower alkyl as defined above. This term isexemplified by groups such as methoxy, ethoxy, n-propoxy, iso-propoxy,n-butoxy, iso-butoxy, t-butoxy, n-hexyloxy, and the like.

The term “alkylthio” refers to the group R—S—, where R is as defined foralkoxy.

The term “alkenyl” refers to a monoradical of a branched or unbranchedunsaturated hydrocarbon group typically having from 2 to 20 carbon atoms(more typically from 2 to 10 carbon atoms, e.g. 2 to 6 carbon atoms) andhaving from 1 to 6 carbon-carbon double bonds, e.g. 1, 2, or 3carbon-carbon double bonds. Typical alkenyl groups include ethenyl (orvinyl, i.e. —CH═CH₂), 1-propylene (or allyl, —CH₂CH═CH₂), isopropylene(—C(CH₃)═CH₂), bicyclo[2.2.1]heptene, and the like. In the event thatalkenyl is attached to nitrogen, the double bond cannot be alpha to thenitrogen.

The term “lower alkenyl” refers to alkenyl as defined above having from2 to 6 carbon atoms.

The term “substituted alkenyl” refers to an alkenyl group as definedabove having 1, 2, 3, 4 or 5 substituents (typically 1, 2, or 3substituents), selected from the group consisting of alkyl, alkenyl,alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy,amino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen,hydroxy, keto, thiocarbonyl, carboxy, carboxyalkyl, arylthio,heteroarylthio, heterocyclylthio, thiol, alkylthio, aryl, aryloxy,heteroaryl, aminosulfonyl, aminocarbonylamino, heteroaryloxy,heterocyclyl, heterocyclooxy, hydroxyamino, alkoxyamino, nitro,—SO-alkyl, —SO-aryl, —SO-heteroaryl, SO₂-aryl and —SO₄-heteroaryl.Unless otherwise constrained by the definition, all substituents mayoptionally be further substituted by 1, 2, or 3 substituents chosen fromalkyl, carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen,CF₃, amino, substituted amino, cyano, and —S(O)_(n)R, where R is alkyl,aryl, or heteroaryl and n is 0, 1 or 2.

The term “alkynyl” refers to a monoradical of an unsaturatedhydrocarbon, typically having from 2 to 20 carbon atoms (more typicallyfrom 2 to 6 carbon atoms) and having e.g. 1, 2, or 3 carbon-carbontriple bonds. Typical alkynyl groups include ethynyl (—C≡CH), propargyl(or propynyl, —C≡CCH3), and the like. In the event that alkynyl isattached to nitrogen, the triple bond cannot be alpha to the nitrogen.

The term “substituted alkynyl” refers to an alkynyl group as definedabove having 1, 2, 3, 4 or 5 substituents (typically 1, 2, or 3substituents), selected from the group consisting of alkyl, alkenyl,alkynyl, alkoxy, cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy,amino, aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen,hydroxy, keto, thiocarbonyl, carboxy, carboxyalkyl, arylthio,heteroarylthio, heterocyclylthio, thiol, alkylthio, aryl, aryloxy,heteroaryl, aminosulfonyl, aminocarbonylamino, heteroaryloxy,heterocyclyl, heterocyclooxy, hydroxyamino, alkoxyamino, nitro,—SO-alkyl, —SO-aryl, —SO-heteroaryl, —SO₂-alkyl, SO₂-aryl and—SO₂-heteroaryl. Unless otherwise constrained by the definition, allsubstituents may optionally be further substituted by 1, 2, or 3substituents chosen from alkyl, carboxy, carboxyalkyl, aminocarbonyl,hydroxy, alkoxy, halogen, CF₃, amino, substituted amino, cyano, and—S(O)_(n)R, where R is alkyl, aryl, or heteroaryl and n is 0, 1 or 2.

The term “aminocarbonyl” refers to the group —C(O)NRR where each R isindependently hydrogen, alkyl, cycloalkyl, aryl, heteroaryl,heterocyclyl or where both R groups are joined to form a heterocyclicgroup (e.g., morpholino). Unless otherwise constrained by thedefinition, all substituents may optionally be further substituted by 1,2, or 3 substituents chosen from alkyl, carboxy, carboxyalkyl,aminocarbonyl, hydroxy, alkoxy, halogen, CF₃, amino, substituted amino,cyano, and —S(O)_(n)R, where R is alkyl, aryl, or heteroaryl and n is 0,1 or 2.

The term “ester” or “carboxyester” refers to the group —C(O)OR, where Ris alkyl, cycloalkyl, aryl, heteroaryl, or heterocyclyl, which may beoptionally further substituted by alkyl, alkoxy, halogen, CF₃, amino,substituted amino, cyano, or —S(O)_(n)Ra, in which Ra is alkyl, aryl, orheteroaryl and n is 0, 1 or 2.

The term “acylamino” refers to the group —NRC(O)R where each R isindependently hydrogen, alkyl, aryl, heteroaryl, or heterocyclyl. Allsubstituents may be optionally further substituted by alkyl, alkoxy,halogen, CF₃, amino, substituted amino, cyano, or —S(O)_(n)R, in which Ris alkyl, aryl, or heteroaryl and n is 0, 1 or 2.

The term “acyloxy” refers to the groups —OC(O)-alkyl, —OC(O)-cycloalkyl,—OC(O)-aryl, —OC(O)-heteroaryl, and —OC(O)-heterocyclyl. Unlessotherwise constrained by the definition, all substituents may optionallybe further substituted by 1, 2, or 3 substituents chosen from alkyl,carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF₃,amino, substituted amino, cyano, and —S(O)_(n)R, where R is alkyl, aryl,or heteroaryl and n is 0, 1 or 2.

The term “aryl” refers to an aromatic carbocyclic group of 6 to 20carbon atoms having a single ring (e.g., phenyl) or multiple rings(e.g., biphenyl), or multiple condensed (fused) rings (e.g., naphthyl,fluorenyl, and anthryl). Typical aryls include phenyl, fluorenyl,naphthyl, anthryl, 1,2,3,4-tetrahydronaphthalene, and the like.

Unless otherwise constrained by the definition for the aryl substituent,such aryl groups can optionally be substituted with 1, 2, 3, 4 or 5substituents (typically 1, 2, or 3 substituents), selected from thegroup consisting of alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl,cycloalkenyl, acyl, acylamino, aryloxy, amino, aminocarbonyl,alkoxycarbonylamino, azido, cyano, halogen, hydroxy, keto, thiocarbonyl,carboxy, carboxyalkyl, arylthio, heteroarylthio, heterocyclylthio,thiol, alkylthio, aryl, aryloxy, heteroaryl, aminosulfonyl,aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclooxy,hydroxyamino, alkoxyamino, nitro, —SO-alkyl, —SO-aryl, —SO-heteroaryl,—SO₂-alkyl, SO₂-aryl and —SO-heteroaryl. Unless otherwise constrained bythe definition, all substituents may optionally be further substitutedby 1, 2, or 3 substituents chosen from alkyl, carboxy, carboxyalkyl,aminocarbonyl, hydroxy, alkoxy, halogen, CF₃, amino, substituted amino,cyano, and —S(O)_(n)R, where R is alkyl, aryl, or heteroaryl and n is 0,1 or 2.

The term “aryloxy” refers to the group aryl-O— wherein the aryl group isas defined above, and includes optionally substituted aryl groups asalso defined above.

The term “arylthio” refers to the group R—S—, where R is as defined foraryl.

The term “amino” refers to the group —NH₂.

The term “substituted amino” refers to the group —NRR where each R isindependently selected from the group consisting of hydrogen, alkyl,cycloalkyl, aryl, heteroaryl and heterocyclyl provided that both Rgroups are not hydrogen, or a group —Y—Z, in which Y is optionallysubstituted alkylene and Z is alkenyl, cycloalkenyl, or alkynyl. Unlessotherwise constrained by the definition, all substituents may optionallybe further substituted by 1, 2, or 3 substituents chosen from alkyl,carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF₃,amino, substituted amino, cyano, and —S(O)_(n)R, where R is alkyl, aryl,or heteroaryl and n is 0, 1 or 2.

The term “carboxyalkyl” refers to the groups —C(O)O-alkyl,—C(O)O-cycloalkyl, where alkyl and cycloalkyl are as defined herein, andmay be optionally further substituted by alkyl, alkenyl, alkynyl,alkoxy, halogen, CF₃, amino, substituted amino, cyano, or —S(O)_(n)R, inwhich R is alkyl, aryl, or heteroaryl and n is 0, 1 or 2.

The term “cycloalkyl” refers to cyclic alkyl groups of from 3 to 20carbon atoms having a single cyclic ring or multiple condensed orbridged rings. Such cycloalkyl groups include, by way of example, singlering structures such as cyclopropyl, cyclobutyl, cyclopentyl,cyclooctyl, and the like, or multiple ring structures such asadamantanyl, and bicyclo[2.2.1]heptane, or cyclic alkyl groups to whichis fused an aryl group, for example indan, and the like.

The term “substituted cycloalkyl” refers to cycloalkyl groups having 1,2, 3, 4 or 5 substituents (typically 1, 2, or 3 substituents), selectedfrom the group consisting of alkyl, alkenyl, alkynyl, alkoxy,cycloalkyl, cycloalkenyl, acyl, acylamino, acyloxy, amino,aminocarbonyl, alkoxycarbonylamino, azido, cyano, halogen, hydroxy,keto, thiocarbonyl, carboxy, carboxyalkyl, arylthio, heteroarylthio,heterocyclylthio, thiol, alkylthio, aryl, aryloxy, heteroaryl,aminosulfonyl, aminocarbonylamino, heteroaryloxy, heterocyclyl,heterocyclooxy, hydroxyamino, alkoxyamino, nitro, —SO-alkyl, —SO-aryl,—SO-heteroaryl, —SO₂-alkyl, SO₂-aryl and —SO₂-heteroaryl. The term“substituted cycloalkyl” also includes cycloalkyl groups wherein one ormore of the annular carbon atoms of the cycloalkyl group is a carbonylgroup (i.e. an oxygen atom is oxo to the ring). Unless otherwiseconstrained by the definition, all substituents may optionally befurther substituted by 1, 2, or 3 substituents chosen from alkyl,carboxy, carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF₃,amino, substituted amino, cyano, and —S(O)_(n)R, where R is alkyl, aryl,or heteroaryl and n is 0, 1 or 2.

The term “halogen” or “halo” refers to fluoro, bromo, chloro, and iodo.

The term “haloalkyl” refers to alkyl of 1-6 carbon atoms substituted by1, 2, 3, 4, 5, or 6 halo atoms.

The term “acyl” denotes a group —C(O)R, in which R is hydrogen,optionally substituted alkyl, optionally substituted cycloalkyl,optionally substituted heterocyclyl, optionally substituted aryl, andoptionally substituted heteroaryl.

The term “heteroaryl” refers to a group comprising 1 to 15 carbon atomsand 1 to 4 heteroatoms selected from oxygen, nitrogen, and sulfur withinat least one ring.

The term “heteroaryl” is generic to the terms “aromatic heteroaryl” and“partially saturated heteroaryl”.

The term “aromatic heteroaryl” refers to a heteroaryl in which at leastone ring is aromatic. Examples of aromatic heteroaryls include pyridyl,thienyl, furanyl, pyrimidyl, imidazolyl, imidazopyridyl, pyranyl,pyrazolyl, pyrzolopyridyl, thiazolyl, thiadiazolyl, isothiazolyl,oxazolyl, isoxazoyl, pyrrolyl, pyridazinyl, pyrazinyl, quinolinyl,isoquinolinyl, benzofuranyl, dibenzofuranyl, dibenzothiophenyl,benzothienyl, indolyl, benzothiazolyl, benzooxazolyl, benzimidazolyl,isoindolyl, benzotriazolyl, purinyl, thianaphthenyl and pyrazinyl.

The term “partially saturated heteroaryl” refers to a heteroaryl havinga structure equivalent to an underlying aromatic heteroaryl which hashad one or more double bonds in an aromatic ring of the underlyingaromatic heteroaryl saturated. Examples of partially saturatedheteroaryls include dihydropyrrole, dihydropyridine,4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine, and the like.

Unless otherwise constrained by the definition for the heteroarylsubstituent, such heteroaryl groups can be optionally substituted with 1to 5 substituents (typically 1, 2, or 3 substituents) selected from thegroup consisting of alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl,cycloalkenyl, acyl, acylamino, acyloxy, amino, aminocarbonyl,alkoxycarbonylamino, azido, cyano, halogen, hydroxy, keto, thiocarbonyl,carboxy, carboxyalkyl (an alkyl ester), arylthio, heteroaryl,heteroarylthio, heterocyclylthio, thiol, alkyl thio, aryl, aryloxy,aralkyl, heteroaryl, aminosulfonyl, aminocarbonylamino, heteroaryloxy,heterocyclyl, heterocyclooxy, hydroxyamino, alkoxyamino, nitro,—SO-alkyl, —SO-aryl, —SO-heteroaryl, —SO₂-alkyl, SO₂-aryl and—SO₂-heteroaryl. Unless otherwise constrained by the definition, allsubstituents may optionally be further substituted by 1, 2, or 3substituents chosen from alkyl, carboxy, carboxyalkyl, aminocarbonyl,hydroxy, alkoxy, halogen, CF₃, amino, substituted amino, cyano, and—S(O)_(n)R, where R is alkyl, aryl, or heteroaryl and n is 0, 1 or 2.Such heteroaryl groups can have a single ring (e.g., pyridyl or furyl)or multiple condensed rings (e.g., indolizinyl, benzothiazole, orbenzothienyl). Examples of nitrogen heterocyclyls and heteroarylsinclude, but are not limited to, pyrrole, imidazole, pyrazole, pyridine,pyrazine, pyrimidine, pyridazine, indolizine, isoindole, indole,indazole, purine, quinolizine, isoquinoline, quinoline, phthalazine,naphthylpyridine, quinoxaline, quinazoline, cinnoline, pteridine,carbazole, carboline, phenanthridine, acridine, phenanthroline,isothiazole, phenazine, isoxazole, phenoxazine, phenothiazine,imidazolidine, imidazoline, and the like as well as N-alkoxy-nitrogencontaining heteroaryl compounds.

The term “heteroaryloxy” refers to the group heteroaryl-O—.

The term “heterocyclyl” refers to a monoradical saturated or partiallyunsaturated group having a single ring or multiple condensed or bridgedrings, having from 1 to 40 carbon atoms and from 1 to 10 hetero atoms,preferably 1, 2, 3 or 4 heteroatoms, selected from nitrogen, sulfur,phosphorus, and/or oxygen within the ring. Heterocyclic groups can havea single ring or multiple condensed rings, and includetetrahydrofuranyl, morpholino, piperidinyl, piperazino, dihydropyridino,4,5,6,7-tetrahydro-1H-benzo[d]imidazole, benzo[d]imidazole,4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine, and the like.

Unless otherwise constrained by the definition for the heterocyclicsubstituent, such heterocyclic groups can be optionally substituted with1, 2, 3, 4 or 5, and preferably 1, 2 or 3 substituents, selected fromthe group consisting of alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl,cycloalkenyl, acyl, acylamino, acyloxy, amino, aminocarbonyl,alkoxycarbonylamino, azido, cyano, halogen, hydroxy, keto, thiocarbonyl,carboxy, carboxyalkyl, arylthio, heteroarylthio, heterocyclylthio,thiol, alkylthio, aryl, aryloxy, heteroaryl, aminosulfonyl,aminocarbonylamino, heteroaryloxy, heterocyclyl, heterocyclooxy,hydroxyamino, alkoxyamino, nitro, —SO-alkyl, —SO-aryl, —SO-heteroaryl,—SO₂-alkyl, SO₂-aryl and —SO₂-heteroaryl. Unless otherwise constrainedby the definition, all substituents may optionally be furthersubstituted by 1-3 substituents chosen from alkyl, carboxy,carboxyalkyl, aminocarbonyl, hydroxy, alkoxy, halogen, CF₃, amino,substituted amino, cyano, and —S(O)_(n)R, where R is alkyl, aryl, orheteroaryl and n is 0, 1 or 2.

The term “thiol” refers to the group —SH.

The term “substituted alkylthio” refers to the group —S-substitutedalkyl.

The term “heteroarylthio” refers to the group —S-heteroaryl wherein theheteroaryl group is as defined above including optionally substitutedheteroaryl groups as also defined above.

The term “sulfoxide” refers to a group —S(O)R, in which R is alkyl,aryl, or heteroaryl. “Substituted sulfoxide” refers to a group —S(O)R,in which R is substituted alkyl, substituted aryl, or substitutedheteroaryl, as defined herein.

The term “sulfone” refers to a group —S(O)₂R, in which R is alkyl, aryl,or heteroaryl. “Substituted sulfone” refers to a group —S(O)₂R, in whichR is substituted alkyl, substituted aryl, or substituted heteroaryl, asdefined herein.

The term “keto” refers to a group —C(O)—. The term “thiocarbonyl” refersto a group —C(S)—. The term “carboxy” refers to a group —C(O)—OH. Theterm “oxo” refers to ═O.

“Optional” or “optionally” means that the subsequently described eventor circumstance may or may not occur, and that the description includesinstances where said event or circumstance occurs and instances in whichit does not.

A “substituted” group includes embodiments in which a monoradicalsubstituent is bound to a single atom of the substituted group (e.g.forming a branch), and also includes embodiments in which thesubstituent may be a diradical bridging group bound to two adjacentatoms of the substituted group, thereby forming a fused ring on thesubstituted group.

A compound of a given Formula (e.g. the “compound of Formula (I)”) isintended to encompass the compounds of the invention as disclosed, andthe pharmaceutically acceptable salts, pharmaceutically acceptableesters, hydrates, polymorphs, and prodrugs of such compounds.Additionally, the compounds of the invention may possess one or moreasymmetric centers, and can be produced as a racemic mixture or asindividual enantiomers or diastereoisomers. The number of stereoisomerspresent in any given compound of a given Formula depends upon the numberof asymmetric centers present (there are 2n stereoisomers possible wheren is the number of asymmetric centers). The individual stereoisomers maybe obtained by resolving a racemic or non-racemic mixture of anintermediate at some appropriate stage of the synthesis, or byresolution of the compound by conventional means. The individualstereoisomers (including individual enantiomers and diastereoisomers) aswell as racemic and non-racemic mixtures of stereoisomers areencompassed within the scope of the present invention, all of which areintended to be depicted by the structures of this specification unlessotherwise specifically indicated.

The invention also included compounds of Formula I in which from 1 to nhydrogens attached to a carbon atom is/are replaced by deuterium, inwhich n is the number of hydrogens in the molecule. Such compoundsexhibit increased resistance to metabolism, and are thus useful forincreasing the half life of any compound of Formula I when administeredto a mammal. See, for example, Foster, “Deuterium Isotope Effects inStudies of Drug Metabolism”, Trends Pharmacol. Sci. 5(12):524-527(1984). Such compounds are synthesized by means well known in the art,for example by employing starting materials in which one or morehydrogens have been replaced by deuterium.

“Isomers” are different compounds that have the same molecular formula.

“Stereoisomers” are isomers that differ only in the way the atoms arearranged in space.

“Enantiomers” are a pair of stereoisomers that are non-superimposablemirror images of each other. A 1:1 mixture of a pair of enantiomers is a“racemic” mixture. The term “(±)” is used to designate a racemic mixturewhere appropriate.

“Diastercoisomers” are stereoisomers that have at least two asymmetricatoms, but which are not mirror-images of each other.

The absolute stereochemistry is specified according to the Cahn IngoldPrelog R S system. When the compound is a pure enantiomer thestereochemistry at each chiral carbon may be specified by either R or S.Resolved compounds whose absolute configuration is unknown aredesignated (+) or (−) depending on the direction (dextro- orlaevorotary) that they rotate the plane of polarized light at thewavelength of the sodium D line.

The term “therapeutically effective amount” refers to an amount that issufficient to effect treatment, as defined below, when administered to amammal in need of such treatment. The therapeutically effective amountwill vary depending upon the subject and disease condition beingtreated, the weight and age of the subject, the severity of the diseasecondition, the manner of administration and the like, which can readilybe determined by one of ordinary skill in the art.

The term “treatment” or “treating” means any treatment of a disease in amammal, including:

-   -   (i) preventing the disease, that is, causing the clinical        symptoms of the disease not to develop;    -   (ii) inhibiting the disease, that is, arresting the development        of clinical symptoms; and/or    -   (iii) relieving the disease, that is, causing the regression of        clinical symptoms.

In many cases, the compounds of this invention are capable of formingacid and/or base salts by virtue of the presence of amino and/orcarboxyl groups or groups similar thereto.

The term “pharmaceutically acceptable salt” of a given compound refersto salts that retain the biological effectiveness and properties of thegiven compound, and which are not biologically or otherwise undesirable.Pharmaceutically acceptable base addition salts can be prepared frominorganic and organic bases. Salts derived from inorganic bases include,by way of example only, sodium, potassium, lithium, ammonium, calciumand magnesium salts. Salts derived from organic bases include, but arenot limited to, salts of primary, secondary and tertiary amines, such asalkyl amines, dialkyl amines, trialkyl amines, substituted alkyl amines,di(substituted alkyl) amines, tri(substituted alkyl) amines, alkenylamines, dialkenyl amines, trialkenyl amines, substituted alkenyl amines,di(substituted alkenyl) amines, tri(substituted alkenyl) amines,cycloalkyl amines, di(cycloalkyl) amines, tri(cycloalkyl) amines,substituted cycloalkyl amines, disubstituted cycloalkyl amine,trisubstituted cycloalkyl amines, cycloalkenyl amines, di(cycloalkenyl)amines, tri(cycloalkenyl) amines, substituted cycloalkenyl amines,disubstituted cycloalkenyl amine, trisubstituted cycloalkenyl amines,aryl amines, diary amines, triaryl amines, heteroaryl amines,diheteroaryl amines, triheteroaryl amines, heterocyclic amines,diheterocyclic amines, triheterocyclic amines, mixed di- and tri-amineswhere at least two of the substituents on the amine are different andare selected from the group consisting of alkyl, substituted alkyl,alkenyl, substituted alkenyl, cycloalkyl, substituted cycloalkyl,cycloalkenyl, substituted cycloalkenyl, aryl, heteroaryl, heterocyclic,and the like. Also included are amines where the two or threesubstituents, together with the amino nitrogen, form a heterocyclic orheteroaryl group.

Specific examples of suitable amines include, by way of example only,isopropylamine, trimethyl amine, diethyl amine, tri(iso-propyl) amine,tri(n-propyl) amine, ethanolamine, 2-dimethylaminoethanol, tromethamine,lysine, arginine, histidine, caffeine, procaine, hydrabamine, choline,betaine, ethylenediamine, glucosamine, N-alkylglucamines, theobromine,purines, piperazine, piperidine, morpholine, N-ethylpiperidine, and thelike.

Pharmaceutically acceptable acid addition salts may be prepared frominorganic and organic acids. Salts derived from inorganic acids includehydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid,phosphoric acid, and the like. Salts derived from organic acids includeacetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid,malic acid, malonic acid, succinic acid, maleic acid, fumaric acid,tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid,methanesulfonic acid, ethanesulfonic acid, p-toluene-sulfonic acid,salicylic acid, and the like.

As used herein, “pharmaceutically acceptable carrier” includes any andall solvents, dispersion media, coatings, antibacterial and antifungalagents, isotonic and absorption delaying agents and the like. The use ofsuch media and agents for pharmaceutically active substances is wellknown in the art. Except insofar as any conventional media or agent isincompatible with the active ingredient, its use in the therapeuticcompositions is contemplated. Supplementary active ingredients can alsobe incorporated into the compositions.

“Coronary diseases” or “cardiovascular diseases” refer to diseases ofthe cardiovasculature arising from any one or more than one of, forexample, heart failure (including congestive heart failure, diastolicheart failure and systolic heart failure), acute heart failure,ischemia, recurrent ischemia, myocardial infarction, arrhythmias, angina(including exercise-induced angina, variant angina, stable angina,unstable angina), acute coronary syndrome, diabetes, and intermittentclaudication.

“Intermittent claudication” means the pain associated with peripheralartery disease. “Peripheral artery disease” or PAD is a type ofocclusive peripheral vascular disease (PVD). PAD affects the arteriesoutside the heart and brain. The most common symptom of PAD is a painfulcramping in the hips, thighs, or calves when walking, climbing stairs,or exercising. The pain is called intermittent claudication. Whenlisting the symptom intermittent claudication, it is intended to includeboth PAD and PVD.

Arrhythmia refers to any abnormal heart rate. Bradycardia refers toabnormally slow heart rate whereas tachycardia refers to an abnormallyrapid heart rate. As used herein, the treatment of arrhythmia isintended to include the treatment of supra ventricular tachycardias suchas atrial fibrillation, atrial flutter, AV nodal reentrant tachycardia,atrial tachycardia, and the ventricular tachycardias (VTs), includingidiopathic ventricular tachycardia, ventricular fibrillation,pre-excitation syndrome, and Torsade de Pointes (TdP).

Where a given group (moiety) is described herein as being attached to asecond group and the site of attachment is not explicit, the given groupmay be attached at any available site of the given group to anyavailable site of the second group. For example, a “loweralkyl-substituted phenyl”, where the attachment sites are not explicit,may have any available site of the lower alkyl group attached to anyavailable site of the phenyl group. In this regard, an “available site”is a site of the group at which a hydrogen of the group may be replacedwith a substituent.

“Pharmaceutically-acceptable” means suitable for use in pharmaceuticalpreparations, generally considered as safe for such use, officiallyapproved by a regulatory agency of a national or state government forsuch use, or being listed in the U.S. Pharmacopoeia or other generallyrecognized pharmacopoeia for use in animals, and more particularly inhumans.

“Pharmaceutically-acceptable carrier” refers to a diluent, adjuvant,excipient, or carrier, other ingredient, or combination of ingredientsthat alone or together provide a carrier or vehicle with which acompound or compounds of the invention is formulated and/oradministered, and in which every ingredient or the carrier as a whole ispharmaceutically acceptable.

“Pharmaceutically-acceptable salt” refers to a salt which may enhancedesired pharmacological activity. Examples ofpharmaceutically-acceptable salts include acid addition salts formedwith inorganic or organic acids, metal salts and amine salts.

Examples of acid addition salts formed with inorganic acids includesalts with hydrochloric acid, hydrobromic acid, sulfuric acid, nitricacid and phosphoric acid. Examples of acid addition salts formed withorganic acids such as acetic acid, propionic acid, hexanoic acid,heptanoic acid, cyclopentanepropionic acid, glycolic acid, pyruvic acid,lactic acid, malonic acid, succinic acid, malic acid, maleic acid,fumaric acid, tartaric acid, citric acid, benzoic acid,o-(4-hydroxy-benzoyl)-benzoic acid, cinnamic acid, mandelic acid,methanesulfonic acid, ethanesulfonic acid, 1,2-ethanedisulfonic acid,2-hydroxyethane-sulfonic acid, benzenesulfonic acid,p-chlorobenzenesulfonic acid, 2-naphthalenesulfonic acid,p-toluenesulfonic acid, camphorsulfonic acid,4-methyl-bicyclo[2.2.2]oct-2-ene1-carboxylic acid, gluco-heptonic acid,4,4′-methylenebis(3-hydroxy-2-naphthoic) acid, 3-phenylpropionic acid,trimethyl-acetic acid, tertiary butylacetic acid, laurylsulfuric acid,gluconic acid, glutamic acid, hydroxy-naphthoic acids, salicylic acid,stearic acid and muconic acid. Examples of metal salts include saltswith sodium, potassium, calcium, magnesium, aluminum, iron, and zincions. Examples of amine salts include salts with ammonia and organicnitrogenous bases strong enough to form salts with carboxylic acids.

“Prodrug” is a compound that, upon in vivo administration, ismetabolized by one or more steps or processes or otherwise converted tothe biologically, pharmaceutically or therapeutically active form of thecompound. To produce a prodrug, the pharmaceutically active compound ismodified such that the active compound will be regenerated by metabolicprocesses. The prodrug may be designed to alter the metabolic stabilityor the transport characteristics of a drug, to mask side effects ortoxicity, to improve the flavor of a drug or to alter othercharacteristics or properties of a drug. By virtue of knowledge ofpharmacodynamic processes and drug metabolism vivo, those of skill inthis art, once a pharmaceutically active compound is known, can designprodrugs of the compound (see, e.g., Nogrady (1985) Medicinal ChemistryA Biochemical Approach, Oxford University Press, New York, pages388-392).

“Polymorph” refers to the different crystal forms of a compound,resulting from the possibility of at least two different arrangements ofthe molecules of the compound in the solid state. Polymorphs of a givencompound will be different in crystal structure but identical in liquidor vapor states. Different polymorphic forms of a given substance maydiffer from each other with respect to one or more physical properties,such as solubility and dissociation, true density, crystal shape,compaction behavior, flow properties, and/or solid state stability.

Nomenclature

Names of compounds of the present invention are provided usingChemBioDraw Ultra 11. Other compounds or radicals may be named withcommon names, or systematic or non-systematic names. The naming andnumbering of the compounds of the invention is illustrated with arepresentative compound of Formula (I)

which is named:

-   N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide.    Combination Therapy

Coronary patients being treated for an acute cardiovascular diseaseevent by administration of ASK1 inhibitors often exhibit diseases orconditions that benefit from treatment with other therapeutic agents.These diseases or conditions can be of the cardiovascular nature or canbe related to pulmonary disorders, metabolic disorders, gastrointestinaldisorders and the like. Additionally, some coronary patients beingtreated for an acute cardiovascular disease event by administration ofan ASK1 inhibitor exhibit conditions that can benefit from treatmentwith therapeutic agents that are antibiotics, analgesics, and/orantidepressants and anti-anxiety agents.

Cardiovascular related diseases or conditions that can benefit from acombination treatment of ASK1 inhibitors with other therapeutic agentsinclude, without limitation, angina, including stable angina, unstableangina (UA), exercised-induced angina, variant angina, arrhythmias,intermittent claudication, myocardial infaretion including non-STEmyocardial infaretion (NSTEMI), heart failure including congestive (orchronic) heart failure, acute heart failure, or recurrent ischemia.

Therapeutic agents suitable for treating cardiovascular related diseasesor conditions include anti-anginals, heart failure agents,antithrombotic agents, antiarrhythmic agents, antihypertensive agents,and lipid lowering agents.

The co-administration of ASK1 inhibitors with therapeutic agentssuitable for treating cardiovascular related conditions allowsenhancement in the standard of care therapy the patient is currentlyreceiving.

Anti-anginals include beta-blockers, calcium channel blockers, andnitrates. Beta blockers reduce the heart's need for oxygen by reducingits workload resulting in a decreased heart rate and less vigorous heartcontraction. Examples of beta-blockers include accbutolol (Sectral),atenolol (Tenormin), betaxolol (Kerlone), bisoprolol/hydrochlorothiazide(Ziac), bisoprolol (Zebeta), carteolol (Cartrol), esmolol (Brevibloe),labetalol (Noiniodyne, Trandate), metoprolol (Lopressor, Toprol XL),nadolol (Corgard), propranolol (Inderal), sotalol (Betapace), andtimolol (Blocadren).

Nitrates dilate the arteries and veins thereby increasing coronary bloodflow and decreasing blood pressure. Examples of nitrates includenitroglycerin, nitrate patches, isosorbide dinitrate, andisosorbide-5-mononitrate.

Calcium channel blockers prevent the normal flow of calciumin to thecells of the heart and blood vessels causing the blood vessels to relaxthereby increasing the supply of blood and oxygen to the heart. Examplesof calcium channel blockers include amlodipine (Norvasc, Lotrel),bepridil (Vascor), diltiazem (Cardizem, Tiazac), felodipine (Plendil),nifedipine (Adalat, Procardia), nimodipine (Nimotop), nisoldipine(Sular), verapamil (Calan, Isoptin, Verelan), and nicardipine.

Agents used to treat heart failure include diuretics, ACE inhibitors,vasodilators, and cardiac glycosides. Diuretics eliminate excess fluidsin the tissues and circulation thereby relieving many of the symptoms ofheart failure. Examples of diuretics include hydrochlorothiazide,metolazone (Zaroxolyn), furosemide (Lasix), bumetanide (Bumex),spironolactone (Aldactone), and eplercnonc (Inspra).

Angiotensin converting enzyme (ACE) inhibitors reduce the workload onthe heart by expanding the blood vessels and decreasing resistance toblood flow. Examples of ACE inhibitors include benazepril (Lotensin),captopril (Capoten), enalapril (Vasotec), fosinopril (Monopril),lisinopril (Prinivil, Zestril), moexipril (Univasc), perindopril(Aceon), quinapril (Accupril), ramipril (Altace), and trandolapril(Mavik).

Vasodilators reduce pressure on the blood vessels by making them relaxand expand. Examples of vasodilators include hydralazine, diazoxide,prazosin, clonidine, and methyldopa. ACE inhibitors, nitrates, potassiumchannel activators, and calcium channel blockers also act asvasodilators.

Cardiac glycosides are compounds that increase the force of the heart'scontractions. These compounds strengthen the pumping capacity of theheart and improve irregular heartbeat activity. Examples of cardiacglycosides include digitalis, digoxin, and digitoxin.

Antithrombotics inhibit the clotting ability of the blood. There arethree main types of antithrombotics—platelet inhibitors, anticoagulants,and thrombolytic agents.

Platelet inhibitors inhibit the clotting activity of platelets, therebyreducing clotting in the arteries. Examples of platelet inhibitorsinclude acetylsalicylic acid (aspirin), ticlopidine, clopidogrel(plavix), dipyridamole, cilostazol, persantine sulfinpyrazone,dipyridamole, indomethacin, and glycoprotein IIb/IIIa inhibitors, suchas abciximab, tirofiban, and eptifibatide (Integrelin). Beta blockersand calcium channel blockers also have a platelet-inhibiting effect.

Anticoagulants prevent blood clots from growing larger and prevent theformation of new clots. Examples of anticoagulants include bivalirudin(Angiomax), warfarin (Coumadin), unfractionated heparin, low molecularweight heparin, danaparoid, lepirudin, and argatroban.

Thrombolytic agents act to break down an existing blood clot. Examplesof thrombolytic agents include streptokinase, urokinase, andtenecteplase (TNI), and tissue plasminogen activator (t-PA).

Antiarrhythmic agents are used to treat disorders of the heart rate andrhythm. Examples of antiarrhythmic agents include amiodarone, quinidine,procainamide, lidocaine, and propafenone. Cardiac glycosides and betablockers are also used as antiarrhythmic agents.

Antihypertensive agents are used to treat hypertension, a condition inwhich the blood pressure is consistently higher than normal.Hypertension is associated with many aspects of cardiovascular disease,including congestive heart failure, atherosclerosis, and clot formation.

Examples of antihypertensive agents include alpha-1-adrenergicantagonists, such as prazosin (Minipress), doxazosin mesylate (Cardura),prazosin hydrochloride (Minipress), prazosin, polythiazide (Minizide),and terazosin hydrochloride (Hytrin); beta-adrenergic antagonists, suchas propranolol (Inderal), nadolol (Corgard), timolol (Blocadren),metoprolol (Lopressor), and pindolol (Visken); centralalpha-adrenoceptor agonists, such as clonidine hydrochloride (Catapres),clonidine hydrochloride and chlorthalidone (Clorpres, Combipres),guanabenz Acetate (Wytensin), guanfacine hydrochloride (Tenex),methyldopa (Aldomet), methyldopa and chlorothiazide (Aldoclor),methyldopa and hydrochlorothiazide (Aldoril); combinedalpha/beta-adrenergic antagonists, such as labetalol (Normodyne,Trandate), Carvedilol (Coreg); adrenergic neuron blocking agents, suchas guanethidine (Ismelin), reserpine (Serpasil); central nervoussystem-acting antihypertensives, such as clonidine (Catapres),methyldopa (Aldomet), guanabenz (Wytensin); anti-angiotensin II agents;ACE inhibitors, such as perindopril (Aceon) captopril (Capoten),enalapril (Vasotec), lisinopril (Prinivil, Zestril); angiotensin-IIreceptor antagonists, such as Candesartan (Atacand), Eprosartan(Teveten), Irbesartan (Avapro), Losartan (Cozaar), Telmisartan(Micardis), Valsartan (Diovan); calcium channel blockers, such asverapamil (Calan, Isoptin), diltiazem (Cardizem), nifedipine (Adalat,Procardia); diuretics; direct vasodilators, such as nitroprusside(Nipride), diazoxide (Hyperstat IV), hydralazine (Apresoline), minoxidil(Loniten), verapamil; and potassium channel activators, such asaprikalim, bimakalim, cromakalim, emakalim, nicorandil, and pinacidil.

Lipid lowering agents are used to lower the amounts of cholesterol orfatty sugars present in the blood. Examples of lipid lowering agentsinclude bezafibrate (Bezalip), ciprofibrate (Modalim), and statins, suchas atorvastatin (Lipitor), fluvastatin (Lescol), lovastatin (Mevacor,Altocor), mevastatin, pitavastatin (Livalo, Pitava) pravastatin(Lipostat), rosuvastatin (Crestor), and simvastatin (Zocor).

In this invention, the patient in need of the ASK1 inhibitor oftensuffers from secondary medical conditions such as one or more of ametabolic disorder, a pulmonary disorder, a peripheral vasculardisorder, or a gastrointestinal disorder. Such patients can benefit fromtreatment of a combination therapy comprising administering to thepatient the compounds of the invention in combination with at least onetherapeutic agent.

Pulmonary disorder refers to any disease or condition related to thelungs. Examples of pulmonary disorders include, without limitation,asthma, chronic obstructive pulmonary disease (COPD), bronchitis, andemphysema.

Examples of therapeutics agents used to treat pulmonary disordersinclude bronchodilators including beta2 agonists and anticholinergics,corticosteroids, and electrolyte supplements. Specific examples oftherapeutic agents used to treat pulmonary disorders includeepinephrine, terbutaline (Brethaire, Bricanyl), albuterol (Proventil),salmeterol (Serevent, Serevent Diskus), theophylline, ipratropiumbromide (Atrovent), tiotropium (Spiriva), methylprednisolone(Solo-Medrol, Medrol), magnesium, and potassium.

Examples of metabolic disorders include, without limitation, diabetes,including type I and type II diabetes, metabolic syndrome, dyslipidemia,obesity, glucose intolerance, hypertension, elevated serum cholesterol,and elevated triglycerides.

Examples of therapeutic agents used to treat metabolic disorders includeantihypertensive agents and lipid lowering agents, as described in thesection “Cardiovascular Agent Combination Therapy” above. Additionaltherapeutic agents used to treat metabolic disorders include insulin,sulfonylureas, biguanides, alpha-glucosidase inhibitors, and incretinmimetics.

Peripheral vascular disorders are disorders related to the blood vessels(arteries and veins) located outside the heart and brain, including, forexample peripheral arterial disease (PAD), a condition that developswhen the arteries that supply blood to the internal organs, arms, andlegs become completely or partially blocked as a result ofatherosclerosis.

Gastrointestinal disorders refer to diseases and conditions associatedwith the gastrointestinal tract. Examples of gastrointestinal disordersinclude gastroesophageal reflux disease (GERD), inflammatory boweldisease (IBD), gastroenteritis, gastritis and peptic ulcer disease, andpancreatitis.

Examples of therapeutic agents used to treat gastrointestinal disordersinclude proton pump inhibitors, such as pantoprazole (Protonix),lansoprazole (Prevacid), esomeprazole (Nexium), omeprazole (Prilosec),rabeprazole; H2 blockers, such as cimetidine (Tagamet), ranitidine(Zantac), famotidine (Pepcid), nizatidine (Axid); prostaglandins, suchas misoprostoL (Cytotec); sucralfate; and antacids.

Patients presenting with an acute coronary disease event may exhibitconditions that benefit from administration of therapeutic agent oragents that are antibiotics, analgesics, antidepressant and anti-anxietyagents in combination with ranolazine.

Antibiotics are therapeutic agents that kill, or stop the growth of,microorganisms, including both bacteria and fungi. Example of antibioticagents include β-Lactam antibiotics, including penicillins(amoxicillin), cephalosporins, such as cefazolin, cefuroxime, cefadroxil(Duricef), cephalexin (Keflex), cephradine (Velosef), cefaclor (Ceder),cefuroxime axtel (Ceftin), cefprozil (Cefzil), loracarbef (Lorabid),cefixime (Suprax), cefpodoxime proxetil (Vantin), ceflibuten (Cedax),cefdinir (Omnicef), ceftriaxone (Rocephin), carbapenems, andmonobactams; tetracyclines, such as tetracycline; macrolide antibiotics,such as erythromycin; aminoglycosides, such as gentamicin, tobramycin,amikacin; quinolones such as ciprofloxacin; cyclic peptides, such asvancomycin, streptogramins, polymyxins; lincosamides, such asclindamycin; oxazolidinoes, such as linezolid; and sulfa antibiotics,such as sulfisoxazole.

Analgesics are therapeutic agents that are used to relieve pain.Examples of analgesics include opiates and morphinomimetics, such asfentanyl and morphine; paracetamol; NSAIDs, and COX-2 inhibitors.

Antidepressant and anti-anxiety agents include those agents used totreat anxiety disorders, depression, and those used as sedatives andtranquillers. Examples of antidepressant and anti-anxiety agents includebenzodiazepines, such as diazepam, lorazepam, and midazolam;enzodiazepines; barbiturates; glutethitnide; chloral hydrate;meprobamate; sertraline (Zoloft, Lustral, Apo-Sertral, Asentra, Gladern,Serlift, Stimuloton); escitalopram (Lexapro, Cipralex); fluoxetine(Prozac, Sarafem, Fluctin, Fontex, Prodep, Fludep, Lovan); venlafaxine(Effexor XR, Efexor); citalopram (Celexa, Cipramil, Talohexane);paroxetine (Paxil, Seroxat, Aropax); trazodone (Desyrel); amitriptyline(Elavil); and bupropion (Wellbutrin, Zyban).

Pharmaceutical Compositions and Administration

Compounds provided in accordance with the present invention are usuallyadministered in the form of pharmaceutical compositions. This inventiontherefore provides pharmaceutical compositions that contain, as theactive ingredient, one or more of the compounds described, or apharmaceutically acceptable salt or ester thereof, and one or morepharmaceutically acceptable excipients, carriers, including inert soliddiluents and fillers, diluents, including sterile aqueous solution andvarious organic solvents, permeation enhancers, solubilizers andadjuvants. The pharmaceutical compositions may be administered alone orin combination with other therapeutic agents. Such compositions areprepared in a manner well known in the pharmaceutical art (see, e.g.,Remington's Pharmaceutical Sciences, Marcel Publishing Co.,Philadelphia, Pa. 17th Ed. (1985); and Modern Pharmaceutics, MarcelDekker, Inc. 3rd Ed. (G. S. Banker & C. T. Rhodes, Eds.)

The pharmaceutical compositions may be administered in either single ormultiple doses by any of the accepted modes of administration of agentshaving similar utilities, for example as described in those patents andpatent applications incorporated by reference, including rectal, buccal,intranasal and transdermal routes, by intra-arterial injection,intravenously, intraperitoneally, parenterally, intramuscularly,subcutaneously, orally, topically, as an inhalant, or via an impregnatedor coated device such as a stent, for example, or an artery-insertedcylindrical polymer.

One mode for administration is parenteral, particularly by injection.The forms in which the novel compositions of the present invention maybe incorporated for administration by injection include aqueous or oilsuspensions, or emulsions, with sesame oil, corn oil, cottonseed oil, orpeanut oil, as well as elixirs, mannitol, dextrose, or a sterile aqueoussolution, and similar pharmaceutical vehicles. Aqueous solutions insaline are also conventionally used for injection, but less preferred inthe context of the present invention. Ethanol, glycerol, propyleneglycol, liquid polyethylene glycol, and the like (and suitable mixturesthereof), cyclodextrin derivatives, and vegetable oils may also beemployed. The proper fluidity can be maintained, for example, by the useof a coating, such as lecithin, by the maintenance of the requiredparticle size in the case of dispersion and by the use of surfactants.The prevention of the action of microorganisms can be brought about byvarious antibacterial and antifungal agents, for example, parabens,chlorobutanol, phenol, sorbic acid, thimerosal, and the like.

Sterile injectable solutions are prepared by incorporating a compoundaccording to the present invention in the required amount in theappropriate solvent with various other ingredients as enumerated above,as required, followed by filtered sterilization. Generally, dispersionsare prepared by incorporating the various sterilized active ingredientsinto a sterile vehicle which contains the basic dispersion medium andthe required other ingredients from those enumerated above. In the caseof sterile powders for the preparation of sterile injectable solutions,the preferred methods of preparation are vacuum-drying and freeze-dryingtechniques which yield a powder of the active ingredient plus anyadditional desired ingredient from a previously sterile-filteredsolution thereof.

Oral administration is another route for administration of compounds inaccordance with the invention. Administration may be via capsule orenteric coated tablets, or the like. In making the pharmaceuticalcompositions that include at least one compound described herein, theactive ingredient is usually diluted by an excipient and/or enclosedwithin such a carrier that can be in the form of a capsule, sachet,paper or other container. When the excipient serves as a diluent, it canbe in the form of a solid, semi-solid, or liquid material (as above),which acts as a vehicle, carrier or medium for the active ingredient.Thus, the compositions can be in the form of tablets, pills, powders,lozenges, sachets, cachets, elixirs, suspensions, emulsions, solutions,syrups, aerosols (as a solid or in a liquid medium), ointmentscontaining, for example, up to 10% by weight of the active compound,soft and hard gelatin capsules, sterile injectable solutions, andsterile packaged powders.

Some examples of suitable excipients include lactose, dextrose, sucrose,sorbitol, mannitol, starches, gum acacia, calcium phosphate, alginates,tragacanth, gelatin, calcium silicate, microcrystalline cellulose,polyvinylpyrrolidone, cellulose, sterile water, syrup, and methylcellulose. The formulations can additionally include: lubricating agentssuch as talc, magnesium stearate, and mineral oil; wetting agents;emulsifying and suspending agents; preserving agents such as methyl andpropylhydroxy-benzoates; sweetening agents; and flavoring agents.

The compositions of the invention can be formulated so as to providequick, sustained or delayed release of the active ingredient afteradministration to the patient by employing procedures known in the art.Controlled release drug delivery systems for oral administration includeosmotic pump systems and dissolutional systems containing polymer-coatedreservoirs or drug-polymer matrix formulations. Examples of controlledrelease systems are given in U.S. Pat. Nos. 3,845,770; 4,326,525;4,902,514; and 5,616,345. Another formulation for use in the methods ofthe present invention employs transdermal delivery devices (“patches”).Such transdermal patches may be used to provide continuous ordiscontinuous infusion of the compounds of the present invention incontrolled amounts. The construction and use of transdermal patches forthe delivery of pharmaceutical agents is well known in the art. See,e.g., U.S. Pat. Nos. 5,023,252, 4,992,445 and 5,001,139. Such patchesmay be constructed for continuous, pulsatile, or on demand delivery ofpharmaceutical agents.

The compositions are preferably formulated in a unit dosage form. Theterm “unit dosage forms” refers to physically discrete units suitable asunitary dosages for human subjects and other mammals, each unitcontaining a predetermined quantity of active material calculated toproduce the desired therapeutic effect, in association with a suitablepharmaceutical excipient (e.g., a tablet, capsule, ampoule). Thecompounds are generally administered in a pharmaceutically effectiveamount. Preferably, for oral administration, each dosage unit containsfrom 1 mg to 2 g of a compound described herein, and for parenteraladministration, preferably from 0.1 to 700 mg of a compound a compounddescribed herein. It will be understood, however, that the amount of thecompound actually administered usually will be determined by aphysician, in the light of the relevant circumstances, including thecondition to be treated, the chosen route of administration, the actualcompound administered and its relative activity, the age, weight, andresponse of the individual patient, the severity of the patient'ssymptoms, and the like.

For preparing solid compositions such as tablets, the principal activeingredient is mixed with a pharmaceutical excipient to form a solidpreformulation composition containing a homogeneous mixture of acompound of the present invention. When referring to thesepreformulation compositions as homogeneous, it is meant that the activeingredient is dispersed evenly throughout the composition so that thecomposition may be readily subdivided into equally effective unit dosageforms such as tablets, pills and capsules.

The tablets or pills of the present invention may be coated or otherwisecompounded to provide a dosage form affording the advantage of prolongedaction, or to protect from the acid conditions of the stomach. Forexample, the tablet or pill can comprise an inner dosage and an outerdosage component, the latter being in the form of an envelope over theformer. The two components can be separated by an enteric layer thatserves to resist disintegration in the stomach and permit the innercomponent to pass intact into the duodenum or to be delayed in release.A variety of materials can be used for such enteric layers or coatings,such materials including a number of polymeric acids and mixtures ofpolymeric acids with such materials as shellac, cetyl alcohol, andcellulose acetate.

Compositions for inhalation or insufflation include solutions andsuspensions in pharmaceutically acceptable, aqueous or organic solvents,or mixtures thereof, and powders. The liquid or solid compositions maycontain suitable pharmaceutically acceptable excipients as describedsupra. Preferably, the compositions are administered by the oral ornasal respiratory route for local or systemic effect. Compositions inpreferably pharmaceutically acceptable solvents may be nebulized by useof inert gases. Nebulized solutions may be inhaled directly from thenebulizing device or the nebulizing device may be attached to a facemasktent, or intermittent positive pressure breathing machine. Solution,suspension, or powder compositions may be administered, preferablyorally or nasally, from devices that deliver the formulation in anappropriate manner.

Synthesis of Compounds of Formula I

The compounds of the invention may be prepared using methods disclosedherein and routine modifications thereof which will be apparent giventhe disclosure herein and methods well known in the art. Conventionaland well-known synthetic methods may be used in addition to theteachings herein. The synthesis of typical compounds described herein,e.g. compounds having structures described by one or more of Formula(I), may be accomplished as described in the following examples. Ifavailable, reagents may be purchased commercially, e.g. from SigmaAldrich or other chemical suppliers.

General Syntheses:

Typical embodiments of compounds in accordance with the presentinvention may be synthesized using the general reaction schemesdescribed below. It will be apparent given the description herein thatthe general schemes may be altered by substitution of the startingmaterials with other materials having similar structures to result inproducts that are correspondingly different. Descriptions of synthesesfollow to provide numerous examples of how the starting materials mayvary to provide corresponding products. Given a desired product forwhich the substituent groups are defined, the necessary startingmaterials generally may be determined by inspection. Starting materialsare typically obtained from commercial sources or synthesized usingpublished methods. For synthesizing compounds which are embodiments ofthe present invention, inspection of the structure of the compound to besynthesized will provide the identity of each substituent group. Theidentity of the final product will generally render apparent theidentity of the necessary starting materials by a simple process ofinspection, given the examples herein

Synthetic Reaction Parameters

The terms “solvent,” “inert organic solvent” or “inert solvent” refer toa solvent inert under the conditions of the reaction being described inconjunction therewith (including, for example, benzene, toluene,acetonitrile, tetrahydrofuran (“THF”), dimethylformamide (“DMF”),chloroform, methylene chloride (or dichloromethane), diethyl ether,methanol, pyridine and the like). Unless specified to the contrary, thesolvents used in the reactions of the present invention are inertorganic solvents, and the reactions are carried out under an inert gas,preferably nitrogen.

One method of preparing compounds of Formula (I) is shown in ReactionScheme I.

A carboxylic acid of formula (1) is reacted with an amine of formula (2)under conditions suitable for the formation of an amide. For example, toa mixture of the compound of formula (1) and formula (2) in an inertsolvent, for example N,N-dimethylformamide, is added(2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate (HATU) and a base, typically N-methyl morpholine,and the mixture is maintained at about room temperature for about 1-12hours. When the reaction is substantially complete, the product ofFormula (I) is isolated by conventional means, for example byfiltration.

The compound of formula (2) is either commercially available or isprepared by means well know in the art. One example of the preparationof a compound of formula (2) in which X¹ is nitrogen is shown inReaction Scheme IA.

Step 1—Preparation of a Compound of Formula (b)

In general, a protected amino ester of formula (a) is reacted withhydrazine hydrate in a protic solvent, for example ethanol. The reactionis carried out at a temperature of about 50-90° C., for about 1-5 hours.When the reaction is substantially complete, the product of formula (b)is isolated by conventional means.

Step 2—Preparation of a Compound of Formula (2)

The compound of formula (b) is then placed in a sealable flask with anamine of formula R¹NH₂ together with a formamide of formula R¹NHCHO inan inert solvent, for example toluene, in the presence of an acid, forexample trifluoroacetic acid. The sealed flask is heated at about 100°C. for about 24 hours. When the reaction is substantially complete, theproduct is isolated by conventional means, for example by flashchromatography.

The product is then reduced under an atmosphere of hydrogen with apalladium catalyst. The reaction is carried out in a protic solvent, forexample ethanol, for about 1-2 hours. When the reaction is substantiallycomplete, the product of formula (2) is isolated by conventional means.

Another example of the preparation of a compound of formula (2) in whichX¹ is nitrogen is shown in Reaction Scheme IB.

Step 1

A mixture of a compound of formula (c) and an amine of formula R¹NH₂ inthe presence of a strong acid, for example trifluoroacetic acid, isplaced in a sealed tube and heated at about 70-110° C. for about 12-36hours. When the reaction is substantially complete, the product isisolated by conventional means.

The protecting group is then removed by conventional treatment with anacid, for example hydrobromic acid in acetic acid, to provide a compoundof formula (2) in which X¹ is nitrogen.

The preparation of compounds of formula (2) in which X¹ is carbon isshown in Reaction Scheme IC.

To a solution of the imidazole derivative of formula (d) in an inertsolvent, for example tetrahydrofuran, at about −50° C. to −80° C., isadded an alkyl derivative, for example n-butyl lithium. The reaction ismaintained at this temperature for about 10-60 minutes, then a solutionof zinc bromide in an inert solvent, for example tetrahydrofuran, isadded, and the mixture allowed to warm to about room temperature forabout 2-3 hours. A solution of the compound of formula (e) in an inertsolvent, for example tetrahydrofuran, is added, and the mixture stirredfor about 10-24 hours. When the reaction is substantially complete, theproduct of formula (2) is isolated by conventional means and purified,for example by chromatography.

An alternative preparation of a compound of Formula (I) is shown inReaction Scheme II.

A carboxylic acid of formula (4) in which Z is a halogen, for examplechloro, bromo, or iodo, is reacted with an amine of formula (2) in thesame manner as described in Reaction Scheme I. The compound of formula(5) thus prepared is then reacted with a boronic acid derivative of R³,for example 3-pyridine boronic acid, in the presence of a phosphineligand of a palladium halide derivative, for example dppf(Pd)Cl₂(diphenylphosphineferrocenepalladium chloride) and a mild base, forexample potassium carbonate. The reaction is typically conducted in amixture of inert solvents, for example a mixture of toluene, water, andethanol, for about 60-100° C. for about 1-4 hours. When the reaction issubstantially complete, the product of Formula (I) is isolated byconventional means, for example by reverse-phase HPLC.

A compound of Formula (I) in which R³ is a non-aromatic ring can beprepared by displacement of Z with a nucleophile, for example an amine,particularly a cyclic amine, or with an alcohol or thiol derivative.Typically, if the nucleophile is an amine, the reaction is carried outusing the amine as a solvent if possible, or the reaction is carried outin a polar aprotic solvent, such as N,N-dimethylformamide,dimethylsulfoxide, or N-methylpyrrolidine, for example. The reactionmixture is maintained at about 80-119° C. for about 1-10 hours. When thereaction is substantially complete, the product of Formula (I) isisolated by conventional means, for example by reverse-phase HPLC.

The construction of the triazole (i.e., where X¹ is N) or imidazole(i.e., where X¹ is C(R⁴)) moiety of compounds of Formula (I) can beaccomplished as a last step. Reaction Scheme IIIA shows the preparationof a compound of Formula (I) in which X¹ is nitrogen.

Conversion of Compound (3) to a Compound of Formula (I)

The compound of formula (3) is placed in a sealable flask with an amineof formula R¹NH₂ together with a formamide of formula R¹NHCHO in aninert solvent, for example toluene, in the presence of an acid, forexample trifluoroacetic acid. The scaled flask is heated at about 100°C. for about 12-48 hours. When the reaction is substantially complete,the product is isolated by conventional means, for example by flashchromatography.

Conversion of Compound (4) to a Compound of Formula (I)

To a suspension of a compound of formula (4) in an inert solvent, forexample toluene, is added N,N-dimethylformamide/N,N-dimethylacetamidecomplex. To this mixture is added a compound of formula R¹NH₂ and acarboxylic acid, for example acetic acid. The mixture is heated at about100-160° C. in a microwave reactor for about 10-60 minutes. When thereaction is substantially complete, the product of Formula (I) isisolated by conventional means, for example by filtration of theprecipitated solid.

Reaction Scheme IIIB shows the preparation of a compound of Formula (I)in which X¹ is carbon.

Step 1

To a solution of an imine of formula (5) in an inert solvent, or amixture of inert solvents, for example a mixture of dimethoxyethane andmethanol, is added toluenesulfonylmethyl isocyanide and an amine offormula R¹NH₂. The mixture is maintained at about 40-60° C. for about6-24 hours, optionally adding a further amount of the isocyanide. Whenthe reaction is substantially complete, the product of formula (6) isisolated by conventional means, for example by chromatography.

Step 2

The compound of formula (6) is then converted to a compound of Formula(I) in which X¹ is carbon in the same manner as described in ReactionScheme II.

The following synthetic schemes represent a summary of specific reactionconditions used in the preparation of intermediates and compounds ofFormula (I) of the present invention.

Step 1

The amino moiety of the compound of formula (1) as an alkyl ester, forexample a methyl ester, is first protected, for example as abenzyloxycarbonyl derivative. In general, the aminoester is dissolved inan inert solvent, for example a mixture of acetone and water, at about0° C., and an amino protecting agent added, for examplebenzyloxycarbonyl chloride. The reaction mixture is allowed to warm toabout room temperature for about 12-30 hours. When the reaction issubstantially complete, the protected amine is isolated by conventionalmeans, for example by addition of water and filtration of the resultantprecipitate.

The protected amine is then dissolved in an inert solvent, for exampleethanol, and hydrazine hydrate added, and the mixture maintained atabout 60-80° C. for about 1-6 hours. When the reaction is substantiallycomplete, the hydrazide is isolated by conventional means.

Step 2

The hydrazide from Step 1 is treated with a compound of the formulaR¹NHCHO and an amine of formula R¹NH₂ in an inert solvent, for exampletoluene, in the presence of a strong acid, for example trifluoroaceticacid. The reaction is conducted in a sealed flask, heating to about80-120° C., for about 12-48 hours. When the reaction is substantiallycomplete, the product is isolated by conventional means. Thebenzyloxycarbonyl protecting group is removed conventionally, forexample by contact with hydrogen in the presaence of a metal catalyst,for example palladium on carbon. The product is isolated and purified byconventional means.

Step 1

To a solution of an amino 1,3,4-oxadiazol-2-yl derivative of formula (f)and a mild base, for example sodium bicarbonate, in a mixture of waterand an inert solvent, for example a mixture of acetone and water atabout 0° C. is added benzylchloroformate, and the mixture maintained atabout room temperature for about 10-60 minutes. When the reaction issubstantially complete, the protected product is isolated byconventional means, for example by addition of water and filtering offthe precipitate.

Step 2

To the product of step 1 in an inert protic solvent, for examplebutanol, is added an amine of formula R¹NH₂ and a strong acid, forexample trifluoroacetic acid. The mixture is maintained at about 90-120°C. in a sealed tube for about 10-24 hours. When the reaction issubstantially complete, the protected product is isolated byconventional means, for example by chromatography on silica gel.

Step 3

The product of step 2 is deprotected by conventional means, for exampleby treatment with a solution of hydrobromic acid in acetic acid. Themixture is maintained at about room temperature for about 12-24 hours.When the reaction is substantially complete, the compound of formula (2)in which X¹ is N is isolated by conventional means.

Step 1

To a suspension of a carboxylic acid of formula (g) in oxalyl chlorideis added N,N-dimethylformamide. The mixture is maintained at about roomtemperature for about 1 hour, then the reaction quenched by addition ofan alcohol, for example isopropanol. The ester thus produced isseparated conventionally, for example by chromatography.

Step 2

To this ester in an inert aqueous solvent mixture, for exampletoluene/water/isopropanol, is added a4,4,5,5-tetramethyl-2-aryl-1,3,2-dioxaborolane derivative and a base,for example potassium carbonate, and dppf(Pd)Cl₂. The mixture ismaintained at about 40-80° C. for about 30 minutes to 4 hours. When thereaction is substantially complete, the product is isolated byconventional means. This ester is converted to a carboxylic acid byconventional means, for example by heating in aqueous hydrochloric acid,to provide a compound of formula (1)

Alternatively, the halide of the compound of formula (g) as an alkylester can first be converted to a boronic acid derivative, for exampleby treatment with4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) in thepresence of dppf(Pd)Cl₂, then reacting the boronic acid derivative thusobtained with an aryl bromide in the presence of dppf(Pd)Cl₂ in an inertaqueous solvent mixture, for example toluene/water/isopropanol and amild base, for example potassium acetate (the Suzuki Reaction).

A carboxylic acid of formula (4) is reacted with an amine of formula(2A) under conditions suitable for the formation of an amide. Forexample, to a mixture of the compound of formula (4) and formula (2A) inan inert solvent, for example N,N-dimethylformamide, is added(2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate (HATU) and a base, typically N-methyl morpholine,and the mixture is maintained at about room temperature for about 1-24hours. When the reaction is substantially complete, the hydrazideproduct is isolated by conventional means, for example by filtration.

A compound of formula (4) is coupled to the compound of formula (f)using standard conditions suitable for the formation of an amide, forexample as shown above in Reaction Scheme VII.

A compound of formula (4) is coupled to the compound of formula (2)using standard conditions suitable for the formation of an amide, forexample as shown above in Reaction Scheme VII.

The hydrazide of formula (3A) is converted to a triazole using theconditions described in Reaction Scheme IIIA.

A compound of formula (4) is coupled to an amino ester using standardconditions suitable for the formation of an amide, for example as shownabove in Reaction Scheme VII.

The halide of the compound of the starting oxadiazole compound is firstconverted to a boronic acid derivative, for example by treatment with4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) in thepresence of dppf(Pd)Cl₂, then reacting the boronic acid derivative thusobtained with an aryl bromide in the presence of dppf(Pd)Cl₂ in an inertaqueous solvent mixture, for example toluene/water/isopropanol and amild base, for example potassium acetate (the Suzuki Reaction).

Step 1

A mixture of paraformaldehyde and an inert solvent, for examplemethanol, is maintained at a temperature of about 0-15° C., and an amineof formula R¹NH₂ is added along with ammonium carbonate, and trimericglyoxal dihydrate. The reaction is maintained at about room temperaturefor about 12-36 hours. When the reaction is substantially complete, theimidazole derivative is isolated by conventional means, for example bydistillation/chromatography.

Step 2

The product form Step 1 is dissolved in an inert solvent, for examplemethylene chloride, and a mild brominating agent added, for example. Thetemperature is maintained at about 5-10° C. for about 1-10 hours. Whenthe reaction is substantially complete, the product of formula (c) isisolated by conventional means, for example by column chromatography.

B. Preparation of 4-Substituted Imidazoles

Ammonia is condensed into a pressure vessel containing formamidineacetate, and a compound of formula R⁴—C(O)CH₂Br added. The pressurevessel is sealed and maintained at about room temperature for about 2-24typically 12 hours. When the reaction is substantially complete, theproduct of formula (c) is isolated by conventional means.

The following examples are provided to illustrate the preparation of thecompounds of the invention, and do not limit this disclosure in any way.

Example 1 Preparation of a Compound of Formula (2) A. Preparation of aCompound of Formula (2) in which R¹ is Cyclopropyl, R² is Hydrogen, X²is N, and X³ and X⁴ are (CR⁴)

Step 1: Preparation of Methyl 6-(benzyloxycarbonylamino)picolinate

A solution of methyl 6-aminopicolinate (10.65 g, 70 mmol, 1 eq) andsodium bicarbonate (13 g, 154 mmol, 2.2 eq) was dissolved in a mixtureof acetone/water (2:1, 1M), and the solution cooled to 0° C.Benzyloxycarbonyl chloride (Cbz-Cl, 11.3 ml, 80.5 mmol, 1.15 eq) wasadded dropwise, and the reaction was warmed to room temperature andstirred for 18 hours. Water (200 mL) was added, and the resultantsuspension was filtered to give a white solid. This solid was dissolvedin methylene chloride, dried over magnesium sulfate, filtered, andconcentrated under reduced pressure to provide methyl6-(benzyloxycarbonylamino)picolinate (17.5 g).

Step 2: Preparation of Benzyl 6-(hydrazinocarbonyl)pyridin-2-ylcarbamate

The methyl 6-(benzyloxycarbonylamino)picolinate from step 1 wasdissolved in ethanol (0.5 M), and hydrazine hydrate (15 mL, 310 mmol,5.0 eq) was added. The solution was heated to reflux and stirred for 2hours, then cooled to room temperature. The solvent was removed underreduced pressure to provide a yellow solid, which was suspended inacetonitrile, filtered, and the solid washed with acetonitrile to yieldbenzyl 6-(hydrazinocarbonyl)pyridin-2-ylcarbamate (17.5 g) as a whitesolid. The filtrate was concentrated and the precipitated solid filteredoff and washed with acetonitrile to provide more benzyl6-(hydrazinecarbonyl)pyridin-2-ylcarbamate. A total of 17.5 g of purematerial was obtained.

Step 3: Preparation of benzyl6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-ylcarbamate

To a sealable flask containing benzyl6-(hydrazinecarbonyl)pyridin-2-ylcarbamate (1.97 g, 6.89 mmol, 1.0 eq)was added N-cyclopropyl formamide (1.8 mL, 20.7 mmol, 3.0 eq),cyclopropylamine (1.4 mL, 20.7 mmol, 3.0 eq), toluene (0.2 M), andtrifluoracetic acid (0.511 mL, 6.89 mmol, 1.0 eq). The flask was sealedand heated to 100° C. for 24 hours. The reaction mixture wasconcentrated under reduced pressure to provide a yellow oil, which waspurified by flash chromatography (Rf=0.44 in 10% methanol/ethyl acetate,gradient flash: 3%→10% methanol in ethyl acetate). The product, whichconsisted of a mixture of the desired compound with cyclopropylformamide, was suspended in acetonitrile, sonicated, and the resultantsuspension filtered to provide benzyl6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-ylcarbamate (680 mg).

Step 4: Preparation of6-(4-Cyclopropyl-4H-[1,2,4]triazol-3-yl)pyridin-2-ylamine

A mixture of benzyl6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-ylcarbamate (660 mg,1.96 mmol, 1.0 eq) and Pd/C (80 mg 10% Pd loading, 40 mg/mmol) wasloaded into a flask and purged with nitrogen. Ethanol (0.4 M) was addedand the flask was charged with hydrogen (1 atm balloon pressure). Thereaction was stirred at room temperature for 90 minutes, and judged tobe complete by TLC. The reaction mixture was filtered through celite,and concentrated under reduced pressure to give 395 mg (95%) of6-(4-cyclopropyl-4H-[1,2,4]triazol-3-yl)-pyridin-2-ylamine. C₁₀H₁₁N₅.202.1 (M+1). ¹H NMR (DMSO) d 8.14 (s, 1H), 7.54 (t, J=8 Hz, 1H), 7.46(d, J=7 Hz, 1H), 6.60 (d, J=8 Hz, 1H), 4.70 (br s, 2H), 3.85-3.88 (m,1H), 1.04-1.07 (m, 2H), 0.85-0.88 (m, 2H).

B. Preparation of other Compounds of Formula (2)

Similarly, optionally replacing methyl 6-aminopicolinate in Example 1A,step 1, and/or optionally replacing cyclopropylamine in Example 1, step3, and following the procedures of Example 1, other compounds of formula(2) are prepared.

Example 2 Alternative Preparation of a Compound of Formula (2) A.Alternative Preparation of a Compound of Formula (2) in which R¹ isCyclopropyl, R² is Hydrogen and X², X³ and X⁴ are (CR⁴)

Step 1: Preparation of benzyl 3-(1,3,4-oxadiazol-2-yl)phenylcarbamate

A solution of 3-(1,3,4-oxadiazol-2-yl)aniline (1 g, 6.2 mmol) and sodiumbicarbonate (1.1 g, 13 mmol) in a 2:1 mixture of acetone/water (10 mL)was cooled to 0° C. Benzylchloroformate (0.92 mL, 6.5 mmol) was addeddropwise over 5 minutes. The reaction mixture was brought to roomtemperature and stirred for 30 minutes at which point LCMS indicatedcompletion of the reaction. The reaction mixture was diluted with waterand filtered on a glass frit to give(3-[1,3,4]Oxadiazol-2-yl-phenyl)-carbamic acid benzyl ester as a whitepowder (1.7 g, 93%). M+1=296.4

Step 2: Preparation of benzyl3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenylcarbamate

A mixture of (3-[1,3,4]Oxadiazol-2-yl-phenyl)-carbamic acid benzyl ester(200 mg, 0.68 mmol), cyclopropylamine (0.5 mL, 7.2 mmol),trifluoroacetic acid (0.05 mL, 0.65 mmol) in anhydrous 1-butanol (3 mL)was heated at 110° C. overnight in a sealed tube. The reaction mixturewas cooled to room temperature and the solvent was removed. The residuewas partitioned between ethyl acetate and saturated sodium bicarbonatesolution, and the aqueous phase was extracted with ethyl acetate.Solvent was removed after drying with sodium sulfate and purified bysilica gel chromatography (rf=0.26 in 20:1 ethyl acetate/methanol) toobtain [3-(4-Cyclopropyl-4H-[1,2,4]triazol-3-yl)-phenyl]-carbamic acidbenzyl ester as a white powder (70 mg, 31%). M+1=335.1

Step 3: Preparation of3-(4-cyclopropyl-4H-[1,2,4]triazol-3-yl)-phenylamine

[3-(4-Cyclopropyl-4H-[1,2,4]triazol-3-yl)-phenyl]-carbamic acid benzylester (60 mg, 0.17 mmol) was dissolved in HBr solution (1 mL, 33% inacetic acid) and the reaction mixture was stirred overnight. The solventwas removed and the residue was neutralized with saturated sodiumbicarbonate solution before being poured into brine. The aqueous phasewas extracted 5 times with ethyl acetate. The organic phase was driedwith sodium sulfate and the solvent was removed to obtain3-(4-cyclopropyl-4H-[1,2,4]triazol-3-yl)-phenylamine as an off-whitepowder (30 mg, 88%). 201.1 (M+1). ¹H NMR of HBr salt (DMSO) d 9.24 (s,1H), 7.50-7.63 (m, 3H), 6.6-8.0 (br, 4H+H₂O), 3.65 ppm (m, 1H), 1.05 (m,4H).

B. Preparation of other Compounds of Formula (2)

Similarly, optionally replacing 3-(1,3,4-oxadiazol-2-yl)aniline inExample 2, step 1, and/or optionally replacing cyclopropylamine inExample 2, step 2, and following the procedures of Example 2, othercompounds of formula (2) are prepared.

Example 3 Preparation of Compounds of Formula (1) A. Preparation of aCompound of Formula (I) in which R³ is4-(1-isopropyl-1H-pyrrolo[3,2-b]pyridin-6-yl, X⁵ is N, and X⁶, X⁷, andX⁸ are (CR⁴)

Step 1: Preparation of isopropyl4-(1H-pyrrolo[3,2-b]pyridin-6-yl)picolinate

N,N-Dimethylformamide (0.3 mL) was added dropwise to a suspension ofoxalyl chloride (6.6 mL, 76 mmol) and 4-chloropicolinic acid (10.0 g,63.5 mmol) in dichloromethane (200 mL). The reaction mixture was stirredfor 1 hour and additional oxalyl chloride (4 mL) andN,N-dimethylformamide (0.2 mL) was added. After a further 30 minutes,isopropanol (100 mL) was slowly added, followed by, after a further 15minutes, solid sodium bicarbonate (12 g). The reaction mixture wasdiluted with 1:1 saturated sodium bicarbonate solution and water, theaqueous phase extracted with dichloromethane (3×100 mL), and solventremoved from the extract under reduced pressure. The residue waspurified by flash chromatography (rf: 0.48 in 2:1 hexanes:ethyl acetate)to give 4-chloropicolinic acid isopropyl ester (11.0 g, 87% yield).200.1 (MH+1).

A mixture of 4-chloropicolinic acid isopropyl ester (1.5 g, 7.5 mmol),6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridine(1.83 g, 7.5 mmol), dppf(Pd)Cl₂ (270 mg, 5 mol %), and potassiumcarbonate (2.0 g, 15 mmol) in degassed toluene (8 mL), degassed water (4mL) and degassed isopropanol (4 mL) was heated at 65° C. for 2 hours.The aqueous phase was discarded and the solvent removed under reducedpressure. The residue was purified by flash chromatography (rf: 0.41 in20:1 ethyl acetate:methanol) to provide isopropyl4-(1H-pyrrolo[3,2-b]pyridin-6-yl)picolinate (1.20 g, 57%) as a yellowpowder. 282.1 (M+1).

Step 2: Preparation of4-(1-isopropyl-1H-pyrrolo[3,2-b]pyridin-6-yl)picolinic acid

Sodium hydride (55 mg, 60% in mineral oil, 1.4 mmol) was added to asolution of isopropyl 4-(1H-pyrrolo[3,2-b]pyridin-6-yl)picolinate (250mg, 0.89 mmol) in N,N-dimethylformamide (3 mL). After stirring for 10minutes, isopropyl iodide was added and the reaction was stirred for 3hours at room temperature. Solvent was removed from the reaction mixtureunder reduced pressure, and the residue dissolved in 2M HCl (3 mL) andheated at 100° C. overnight. The crude reaction mixture was purified byreverse-phase HPLC to give4-(1-isopropyl-1H-pyrrolo[3,2-b]pyridin-6-yl)picolinic acid (50 mg,20%). 282.1 (M+1).

B. Preparation of other Compounds of Formula (I)

Similarly, optionally replacing 4-chloropicolinic acid in Example 3,step 1 with other aromatic carboxylic acids, and/or optionally replacing6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[3,2-b]pyridinein Example 3, step 1 with similar boron complexes, and optionallyreplacing isopropyl iodide with other alkyl halides in Example 3, step2, and following the procedures of Example 3, other compounds of formula(1) are prepared.

Example 4 Preparation of Compounds of Formula (1) A. Preparation of aCompound of Formula (1) in which R³ is (2-hydroxypropan-2-yl)pyridine,X⁵ is N, and X⁶, X⁷, and X⁸ are (CR⁴)

Step 1: Preparation of 2-isopropoxycarbonyl)pyridin-4-ylboronic acid

A suspension of 4-chloropicolinic acid isopropyl ester (2.0 g, 10 mmol),bis-pinacolatodiboron (3.05 g, 12 mmol), dppf(Pd)Cl₂ (150 mg, 2.5 mol%), potassium acetate (1.5 g, 15 mmol) in degassed N,N-dimethylformamide(10 mL) was heated at 80° C. for 4 hours. The solvent was removed underreduced pressure, and the crude mixture thus obtained was used in Step 2without purification. 210.1 (M+1).

Step 2: Preparation of isopropyl6-(2-hydroxypropan-2-yl)-3,4′-bipyridine-2′-carboxylate

A mixture of crude 2-(isopropoxycarbonyl)pyridin-4-ylboronic acid (700mg, 1.0 mmol), dppf(Pd)Cl₂ (40 mg, 5 mol %), potassium carbonate (280mg, 2.0 mmol) and 2-(5-bromopyridin-2-yl)propan-2-ol (216 mg, 1.0 mmol)in degassed toluene (3 mL), degassed water (1 mL) and degassedisopropanol (1 mL) was heated at 85° C. for 1 hour. The aqueous layerwas discarded and the solvent removed under reduced pressure. Theresidue was purified by flash chromatography (rf: 0.53 in 20:1 ethylacetate:methanol) to give isopropyl6-(2-hydroxypropan-2-yl)-3,4′-bipyridine-2′-carboxylate (140 mg, 47%yield). 301.1 (M+1).

Step 3: Preparation of6-(2-hydroxypropan-2-yl)-3,4′-bipyridine-2′-carboxylic acid

A solution of isopropyl6-(2-hydroxypropan-2-yl)-3,4′-bipyridine-2′-carboxylate (140 mg, 0.47mmol) in 1 M hydrochloric acid (2 mL) was heated at 100° C. overnight.The solvent was removed under reduced pressure to give6-(2-hydroxypropan-2-yl)-3,4′-bipyridine-2′-carboxylic acidhydrochloride salt as a white powder (106 mg, 87%). 259.1 (M+1).

B. Preparation of other Compounds of Formula (1)

Similarly, optionally replacing 4-chloropicolinic acid isopropyl esterin Example 4, step 1 with other aromatic carboxylic esters, and/oroptionally replacing bis-pinacolatodiboron in Example 4, step 1 withsimilar boron complexes, and optionally replacing2-(5-bromopyridin-2-yl)propan-2-ol with other haloaryl derivatives inExample 4, step 2, and following the procedures of Example 4, othercompounds of formula (1) are prepared.

Example 5 Preparation of Compounds of Formula (3) A. Preparation of aCompound of Formula (3) in which X² and X⁵ are N, X³, X⁴, X⁶, X⁷, and X⁸are (CR⁴), and R² is Hydrogen, and R³ is Chloro

Step 1: Preparation of methyl 6-(4-chloropicolinamide)picolinate

A solution of 4-chloro-pyridine-2-carboxylic acid (16.3 g, 103 mmol),methyl 6-aminopicolinate (3.0 g, 18.6 mmol),(2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethylumniumhexafluorophosphate (HATU, 41.1 g, 108 mmol), and N-methyl morpholine(12.5 mL, 108 mmol) in N,N-dimethylformamide was stirred at roomtemperature for 12 hours. The solvent was removed under reducedpressure, and the residue suspended in acetonitrile. The solid thusobtained was isolated by filtration, washed with water (80 mL),acetonitrile (80 mL) and diethyl ether (80 m L) and dried under reducedpressure to afford6-[(4-chloro-pyridine-2-carbonyl)-amino]-pyridine-2-carboxylic acidmethyl ester as a white powder (25.6, 93% yield).

Step 2: Preparation of4-chloro-N-(6-(hydrazinecarbonyl)pyridin-2-yl)picolinamide

The crude 6-[(4-chloro-pyridine-2-carbonyl)-amino]-pyridine-2-carboxylicacid methyl ester from the previous step (25.3 g, 87.8 mmol) wassuspended in ethanol (200 mL), and hydrazine hydrate (21.3 mL, 439 mmol)was added. The reaction mixture was refluxed for 4 hours, solventremoved under reduced pressure, and the residue suspended inacetonitrile and collected by filtration. The solids were washed withacetonitrile (2×100 mL) and diethylether (2×100 mL), and dried underreduced pressure to afford 25.3 g (92% yield) of4-chloro-N-(6-(hydrazinecarbonyl)pyridin-2-yl)picolinamide as a whitesolid.

B. Preparation of other Compounds of Formula (3)

Similarly, optionally replacing 4-chloro-pyridine-2-carboxylic acid inExample 5 step 1, with other aromatic carboxylic esters, and/oroptionally replacing methyl 6-aminopicolinate in Example 5, step 1, withother aromatic aminoesters, and following the procedures of Example 5,other compounds of formula (3) are prepared.

Example 6 Preparation of Compounds of Formula (4) Preparation of aCompound of Formula (4) in which X², X³, X⁴, X⁶, X⁷, and X⁸ are (CR⁴),X⁵ is N, R² is Hydrogen, and R³ is Bromo A. Preparation ofN-(3-(1,3,4-oxadiazol-2-yl)phenyl)-4-bromopicolinamide

A solution of 4-bromopyridine-2-carboxylic acid (3.76 g, 18.6 mmol),3-[1,3,4]oxadiazol-2-yl-phenylamine (3.0 g, 18.6 mmol),(2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate (HATU) (7.1 g, 18.7 mmol), and diisopropylethylamine(15 mL) in N,N-dimethylformamide was stirred at room temperature for 1hour. The solvent was removed under reduced pressure, and the residuewas stirred with acetonitrile (40 mL) and water (40 mL). The solid thusobtained was isolated by filtration, washed with water (20 mL),acetonitrile (20 mL) and diethyl ether (40 mL), and dried under reducedpressure to give N-(3-(1,3,4-oxadiazol-2-yl)phenyl)-4-bromopicolinamideas a white powder (5.2 g, 15.0 mmol, 81% yield).

B. Preparation of other Compounds of Formula (4)

Similarly, optionally replacing 4-bromopyridine-2-carboxylic acid withother haloaromatic carboxylic acids, and/or optionally replacing3-[1,3,4]oxadiazol-2-yl-phenylamine with other3-[1,3,4]oxadiazol-2-yl-aromatic amines, and following the procedures ofExample 6, other compounds of formula (4) are prepared.

Example 7 Preparation of Compounds of Formula (5) Preparation of aCompound of Formula (5) in which R¹ is Cyclopropyl, R² is Hydrogen, X¹,X², and X⁵ are N, X³, X⁴, X⁶, and X⁸ are (CR⁴), X⁷ is C(CH₃), and Z isChloro A. Preparation of4-Chloro-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-methylpicolinamide

A solution of 4-chloro-5-methylpicolinic acid (159 mg, 0.924 mmol),6-(4-Cyclopropyl-4H-[1,2,4]triazol-3-yl)-pyridin-2-ylamine (169 mg,0.840 mmol), (2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate (HATU) (383 mg, 1.01 mmol), and N-methylmorpholine(11 μL, 1.01 mmol) in N,N-dimethylformamide was stirred at 65° C. for1.2 hours. The solvent was removed under reduced pressure, the residuewas suspended in acetonitrile, and the solid product was isolated byfiltration, washed with water (80 mL), acetonitrile (80 mL), diethylether (80 mL), and dried under vacuum to afford4-chloro-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-methylpicolinamideas a white powder (140 mg, 47% yield).

B. Preparation of other Compounds of Formula (5)

Similarly, optionally replacing 4-chloro-5-methylpicolinic acid withother halo aromatic carboxylic acids of formula (4), and/or optionallyreplacing 6-(4-cyclopropyl-4H-[1,2,4]triazol-3-yl)-pyridin-2-ylaminewith other compounds of formula (2), and following the procedures ofExample 7, other compounds of formula (5) are prepared.

Example 8 Alternative Preparation of Compounds of Formula (5)Preparation of a Compound of Formula (5) in which R¹ is Cyclopropyl, R²is Hydrogen, X¹, X², and X⁵ are N, X³, X⁴, X⁶, X⁷, and X⁸ are (CR⁴), andZ is Chloro A. Preparation4-chloro-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)picolinamide

To a suspension of4-chloro-N-(6-(hydrazinecarbonyl)pyridin-2-yl)picolinamide (1.00 g, 3.43mmol) in toluene (0.20 M) was added a mixture ofN,N-dimethylformamide•N-dimethylacetamide (1.14 mL, 8.56 mmol),cyclopropylamine (873 μL, 13.7 mmol), and acetic acid (194 μL, 3.43mmol). The reaction mixture was heated to 150° C. for 30 minutes in amicrowave reactor. The reaction product was concentrated under reducedpressure, and the residue was suspended in acetonitrile/diethylether(1.5 mL, 1:1 ratio), filtered, and the solid washed withacetonitrile/diethylether (2×10 mL). The filtrate was concentrated andthe solid thus obtained was purified as above. The combined solids weredried under reduced pressure to afford 842 mg (72% yield) of4-chloro-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)picolinamideas a white solid.

B. Preparation of other Compounds of Formula (5)

Similarly, optionally replacing4-chloro-N-(6-(hydrazinecarbonyl)pyridin-2-yl)picolinamide with othercompounds of formula (3), and/or optionally replacing cyclopropylaminewith other amines of formula R¹NH₂, and following the procedures ofExample 8, other compounds of formula (5) are prepared.

Example 9 Alternative Preparation of Compounds of Formula (3)Preparation of a Compound of Formula (3) in which X² and X⁵ are N, X³,X⁴, X⁶, X⁷, and X⁸ are (CR⁴), and R³ is 2-cyclopropylpyridine A.Preparation of6-cyclopropyl-N-(6-(hydrazinecarbonyl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide

Step 1

A solution of 6-cyclopropyl-3,4′-bipyridine-2′-carboxylic acidhydrochloride salt (1.73 g, 6.25 mmol), 6-aminopicolinate methyl ester(1.05 g, 6.87 mmol),(2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate (HATU, 2.85 g, 7.50 mmol), and N-methylmorpholine(1.51 mL, 13.8 mmol) in N,N-dimethylformamide was stirred at roomtemperature for 4 hours. The solvent was removed under reduced pressure,and the residue suspended in acetonitrile. The solid thus obtained wasisolated by filtration, washed with water (80 mL), acetonitrile (80 mL)and diethyl ether (80 mL) and dried under reduced pressure to affordmethyl 6-(6-cyclopropyl-3,4′-bipyridine-2′-carboxamido)picolinate as awhite powder, which was used directly in the next step.

Step 2

The methyl 6-(6-cyclopropyl-3,4′-bipyridine-2′-carboxamido)picolinatefrom the previous step were suspended in ethanol (20 mL), hydrazinehydrate (700 μL, 14.4 mmol) was added, and the reaction was heated torelfux for 4 hours. The reaction mixture was concentrated and theresultant solids were suspended in acetronitrile and collected byfiltration. The solids were washed with acetonitrile (2×100 mL) anddiethyl ether (2×100 mL), and dried under reduced pressure to afford1.21 g (47% yield) of6-cyclopropyl-N-(6-(hydrazinecarbonyl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamideas a white solid.

B. Preparation of other Compounds of Formula (3)

Similarly, optionally replacing6-cyclopropyl-3,4′-bipyridine-2′-carboxylic acid hydrochloride in Step 1with other equivalent carboxylic acids, and/or optionally replacing6-aminopicolinate methyl ester in step 1 with other amino esters, andfollowing the procedures of Example 9, other compounds of formula (3)are prepared.

Example 10 Alternative Preparation of Compounds of Formula (4)Preparation of a Compound of Formula (4) in which X², X³, X⁴, X⁶, X⁷ andX⁸ are (CR⁴), X⁵ is N, R² is Hydrogen, and R³ is 2-cyclopropylpyridineA. Preparation ofN-(3-(1,3,4-oxadiazol-2-yl)phenyl)-6-cyclopropyl-3,4′-bipyridine-2′-carboxamide

A suspension of N-(3-(1,3,4-oxadiazol-2-yl)phenyl)-4-bromopicolinamide(3.0 g, 8.7 mmol),2-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine(2.25 g, 9.2 mmol), dppf(Pd)Cl₂ (320 mg, 5 mol %), potassium carbonate(2.4 g, 17 mmol) in degassed toluene (10 mL), degassed water (10 mL) anddegassed isopropanol (10 mL) was heated at 85° C. for 4 hours. Thesolvent was removed under reduced pressure and the residue was suspendedand sonicated in methanol (40 mL) before being filtered and washed withmethanol (10 mL). The grey powder was then suspended and sonicated inwater (40 mL) before being filtered and washed with water (10 mL),methanol (10 mL) and diethyl ether (10 mL) to give6-cyclopropyl-[3,4′]bipyridinyl-2′-carboxylic acid(3-[1,3,4]oxadiazol-2-yl-phenyl)-amide (3.0 g, 90%). 384.1 (M+1).

B. Preparation of other Compounds of Formula (4)

Similarly, optionally replacingN-(3-(1,3,4-oxadiazol-2-yl)phenyl)-4-bromopicolinamide with otherequivalent aromatic halo derivatives, and/or optionally replacing2-cyclopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridinewith other boron complexes, and following the procedures of Example 10,other compounds of formula (4) are prepared.

Example 11 Preparation of Compounds of Formula (d) Preparation of aCompound of Formula (d) in which R¹ is Cyclopropyl

Step 1

To a 200 ml round bottomed flask was added 4.08 g (136 mmol) ofparaformaldehyde and 20 mL of methanol. After cooling the mixture to0-5° C., the following were added in order, 7.36 g (129 mmol)cyclopropyl amine, 10 mL methanol, 6.20 g (65 mmol) ammonium carbonate,10 mL methanol, 9.07 g (43.1 mmol) trimeric glyoxal dihydrate and 25 mLmethanol. The reaction was stirred overnight at room temperature. Thevolatiles were removed by rotary evaporation, with special care not toheat the mixture as the product is volatile. The mixture was thendistilled at 15-20 torr and the product co-distilled with anotherimpurity at 90-95° C. This mixture was chromatographed on silica gel(1:1 hexanes/ethyl acetate, then 7% methanol in methylene chloride) toafford 1.76 g (25% yield) of 1-cyclopropyl-1H-imidazole as a yellow oil.

Step 2

Cyclopropyl-1H-imidazole (1.18 g, 10.9 mmol) was dissolved in methylenechloride (0.1 M), cooled to 5-10° C., and1,3-dibromo-5,5-dimethylhydantoin (1.59 g, 5.57 mmol) was added. Thetemperature was maintained between 5-10° C. and the reaction was stirredfor 2 hours. Solvent was removed from the reaction mixture under reducedpressure, and the residue was purified by column chromatography (elutingwith 1%-7% methanol in methylene chloride, 5% methanol/methylenechloride) to afford 620 mg (37% yield) of5-bromo-1-cyclopropyl-1H-imidazole.

B. Preparation of other Compounds of Formula (d)

Similarly, replacing cyclopropylamine with other amines of formulaR¹NH₂, and following the procedures of Example 11, other compounds offormula (d) are prepared.

Example 12 Preparation of 4-alkyl Substituted Imidazoles A. Preparationof 4-cyclopropyl-1H-imidazole

Ammonia (˜75 mL) was condensed into a pressure vessel containingformamidine acetate (60 g, 0.58 mol) and a stir bar at −78° C.2-bromo-1-cyclopropyl-ethanone (10.2 g, 0.063 mol) was added dropwiseand the pressure vessel was sealed and warmed to room temperature andstilled for 12 hours. The reaction mixture was then cooled to −78° C.before being carefully opened. The cooling bath was removed and theammonia was allowed to evaporate. The residue was dissolved in 100 mL ofwater and 20 mL saturated sodium bicarbonate solution, and then solidsodium chloride was added until the solution was saturated. This mixturewas extracted with ethyl acetate (4×100 mL) and the organic phase wasdried with sodium sulfate before being evaporated to yield4-cyclopropyl-1H-imidazole as a yellow oil (70-80% purity, 5.3 g, 78%yield, M+1=109.1) which was used without further purification.Reverse-phase HPLC (0.1% HCl H₂0, MeCN) of the crude compound gave ananalytically pure sample (1.0 g). ¹H NMR of HCl salt (DMSO) d 8.96 (s,1H), 7.38 (s, 1H), 1.96 (m, 1H), 0.97 (m, 2H), 0.79 (m, 2H).

B. Preparation of other Compounds of Formula (d)

Similarly, replacing 2-bromo-1-cyclopropyl-ethanone with otherhaloethanones of formula RC(O)CH₂X, where R is alkyl and X is halo, andfollowing the procedures of Example 12, other 4-alkylimidazoles areprepared.

Example 13 Preparation of Compounds of Formula (I) via the SuzukiReaction A. Preparation of a Compound of Formula (I) in which X², X³,X⁴, X⁶, X⁷ and X⁸ are (CR⁴), X¹ and X⁵ are N, R¹ is Cyclopropyl, R² isHydrogen, and R³ is Pyridin-3-yl

A suspension of4-bromo-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide(120 mg, 0.31 mmol), 3-pyridine boronic acid (77 mg, 0.62 mmol),dppf(Pd)Cl₂ (23 mg, 0.03 mmol), potassium carbonate (86 mg, 0.62 mmol)in degassed toluene (2 mL), degassed water (1 mL) and degassed ethanol(1 mL) was heated at 100° C. for 1 hour. The solvent was removed underreduced pressure and the residue purified by reverse-phase HPLC, to giveN-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamideas a white powder (58 mg, 0.15 mmol, 48% yield). C₂₂H₁₈N₆O. 383.1 (M+1).¹H NMR (DMSO) d 10.98 (s, 1H), 9.12 (d, J=1.6 Hz, 1H), 8.87 (d, J=4.8Hz, 1H), 8.72 (dd, J=4.8, 1.2 Hz, 1H), 8.63 (s, 1H), 8.60 (s, 1H), 8.48(d, J=1.2 Hz, 1H), 8.34 (m, 1H), 8.11 (m, 2H), 7.69 (d, J=8.0 Hz, 1H),7.59 (m, 2H), 3.66 (m, 1H), 1.09 (m, 2H), 0.94 (m, 2H).

B. Similarly, following the procedures as described in Examples 1-13where appropriate, the following compounds of Formula (I) were prepared:

N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₀H₁₆N₆O. 357.1 (M+1). ¹H NMR (DMSO) d 10.98 (s, 1H), 9.11 (d, J=1.6Hz, 1H), 8.87 (d, J=5.2 Hz, 1H), 8.73 (dd, J=4.8, 1.6 Hz, 1H), 8.59 (s,1H), 8.49 (d, J=1.2 Hz, 1H), 8.34 (m, 2H), 8.11 (m, 2H), 7.58 (m, 3H),3.81 (s, 3H).

N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-2-phenylisonicotinamide

C₂₁H₁₇N₅O. 356.1 (M+1). ¹H NMR (DMSO) d 10.76 (s, 1H), 8.88 (d, J=5.2Hz, 1H), 8.60 (s, 1H), 8.43 (s, 1H), 8.18-8.22 (m, 3H), 7.98 (d, J=7.6Hz, 1H), 7.83 (d, J=7.6 Hz, 1H), 7.46-7.62 (m, 5H), 3.79 (s, 3H).

5-methoxy-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₁H₁₈N₆O₂. 387.2 (M+1). ¹H NMR (DMSO) d 10.98 (s, 1H), 8.86 (d, J=4.8Hz, 1H), 8.68 (d, J=1.6 Hz, 1H), 8.59 (s, 1H), 8.51 (d, J=1.2 Hz, 1H),8.44 (d, J=2.4 Hz, 1H), 8.35 (s, 1H), 8.12 (m, 2H), 7.88 (t, J=2.2 Hz,1H), 7.55 (m, 2H), 3.96 (s, 3H), 3.81 (s, 3H).

5-acetamido-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₂H₁₉N₇O₂. 414.1 (M+1). ¹H NMR (DMSO) d 10.99 (s, 1H), 10.39 (s, 1H),8.87 (d, J=5.2 Hz, 1H), 8.84 (d, J=2.4 Hz, 1H), 8.79 (d, J=2.0 Hz, 1H),8.59 (s, 1H), 8.53 (s, 1H), 8.41 (s, 1H), 8.36 (s, 1H), 8.12 (d, J=7.6Hz, 1H), 8.06 (dd, J=5.4, 1.8 Hz, 1H), 7.56 (m, 2H), 3.81 (s, 3H), 2.13(s, 3H).

4-(imidazo[1,2-a]pyridin-3-yl)-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-picolinamide

C₂₂H₁₇N₇O. 396.1 (M+1). ¹H NMR (DMSO) d 10.98 (s, 1H), 8.84 (m, 2H),8.59 (s, 1H), 8.42 (d, J=0.8 Hz, 1H), 8.35 (s, 1H), 8.20 (s, 1H), 8.14(m, 1H), 8.04 (dd, J=5.2, 1.6 Hz, 1H), 7.76 (d, J=9.2 Hz, 1H), 7.54 (m,2H), 7.44 (m, 1H), 7.12 (dt, J=7.2, 0.8 Hz, 1H), 3.81 (s, 3H).

N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-methylpiperazin-1-yl)picolinamide

C₂₀H₁₃N₇O. 378.1 (M+1). ¹H NMR (DMSO) d 10.80 (s, 1H), 8.58 (s, 1H),8.30-8.32 (m, 2H), 8.02-8.09 (m, 1H), 7.57 (d, J=2.4 Hz, 1H), 7.48-7.56(m, 2H), 7.08 (dd, J=2.4, 6 Hz, 1H), 3.79 (s, 3H), 3.42 (t, J=4.8 Hz,4H), 2.44 (t, J=4.8 Hz, 4H), 2.23 (s, 3H).

N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(3-oxopiperazin-1-yl)picolinamide;

C₁₉H₁₉N₇O₂. 378.1 (M+1). ¹H NMR (DMSO) d 10.81 (s, 1H), 8.59 (s, 1H),8.33 (d, J=6 Hz, 1H), 8.27-8.32 (m, 2H), 8.15 (br s, 1H), 8.05-8.09 (m,1H), 7.48-7.56 (m, 3H), 7.03 (dd, J=2.8, 5.6 Hz, 1H), 3.96 (s, 2H), 3.79(s, 3H), 3.63 (t, J=4.8 Hz, 2H), 3.33-3.35 (m, 2H).

4-(3-aminopyrrolidin-1-yl)-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide

C₁₉H₂₁H₇O. 364.1 (M+1). ¹H NMR (CD₃OD) d 8.59 (s, 1H), 8.49 (s, 1H),8.30 (d, J=6 Hz, 1H), 8.23-8.25 (m, 1H), 7.60 (t, J=8 Hz, 1H), 7.51 (d,J=7.6 Hz, 1H), 7.60 (t, J=8 Hz, 1H), 7.51 (d, J=7.6 Hz, 1H), 7.40 (d,J=2.4 Hz, 1H), 6.73 (dd, J=2.4, 6 Hz, 1H), 4.04-4.09 (m, 1H), 3.86 (s,3H), 3.78 (dd, J=2, 7.2 Hz, 1H), 3.63-3.72 (m, 1H) 3.47-3.60 (m, 2H),2.45-2.56 (m, 1H), 2.17-2.25 (m, 1H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-phenylpicolinamide

C₂₃H₁₉N₅O. 382.2 (M+1). ¹H NMR (CD₃OD) d 8.71 (d, J=4.8 Hz, 1H), 8.60(s, 1H), 8.44 (d, J=1.2 Hz, 1H), 7.92-7.95 (m, 1H), 7.84 (dd, J=2, 5.2Hz, 1H), 7.78 (d, J=7.2 Hz, 1H), 7.66 (d, J=7.2 Hz, 2H), 7.66 (d, J=7.2Hz, 1H), 7.56 (t, J=8 Hz, 1H), 7.45-7.53 (m, 3H), 3.64 (m, 1H),1.14-1.19 (m, 2H), 0.95-1.00 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-methoxy-3,4′-bipyridine-2′-carboxamide

C₂₃H₂₀N₆O₂. 413.4 (M+1). ¹H NMR (DMSO) d 10.93 (s, 1H), 8.80 (d, J=4.8Hz, 1H), 8.76 (d, J=2.0 Hz, 1H), 8.63 (s, 1H), 8.58 (s, 1H), 8.43 (d,J=1.2 Hz, 1H), 8.28 (dd, J=4.8, 2.8 Hz, 1H), 8.05 (m, 2H), 7.68 (d,J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 7.01 (d, J=8.0 Hz, 1H), 3.94 (s,3H), 3.67 (m, 1H), 1.09 (m, 2H), 0.95 (m, 2H).

6-amino-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₂H₁₉N₇O. 398.1 (M+1). ¹H NMR (DMSO) d 10.88 (s, 1H), 8.69 (d, J=5.2Hz, 1H), 8.62 (s, 1H), 8.58 (s, 1H), 8.53 (d, J=2.0 Hz, 1H), 8.33 (d,J=1.2 Hz, 1H), 8.06 (d, J=8.8 Hz, 1H), 7.94 (m, 2H), 7.68 (d, J=8.0 Hz,1H), 7.54 (t, J=8.0 Hz, 1H), 6.58 (d, 8.8 Hz, 1H), 6.47 (s, 2H), 3.66(m, 1H), 1.08 (m, 2H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(pyrimidin-5-yl)picolinamide

C₂₁H₁₇N₇O. 384.1 (M+1). ¹H NMR (DMSO) d 10.99 (s, 1H), 9.37 (s, 2H),9.33 (s, 1H), 8.91 (d, J=5.2 Hz, 1H), 8.63 (s, 1H), 8.58 (m, 2H), 8.18(dd, J=4.8, 1.6 Hz, 1H), 8.08 (d, J=4.8 Hz, 1H), 7.69 (d, J=8.0 Hz, 1H),7.56 (t, J=8.0 Hz, 1H), 3.67 (m, 1H), 1.09 (m, 2H), 0.95 (m, 2H).

4-(2-aminopyrimidin-5-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide

C₂₁H₁₈N₈O. 399.1 (M+1). ¹H NMR (DMSO) d 10.91 (s, 1H), 8.85 (s, 2H),8.74 (d, J=4.8 Hz, 1H), 8.63 (s, 1H), 8.58 (s, 1H), 8.40 (d, J=1.2 Hz,1H), 8.06 (d, J=9.2 Hz, 1H), 8.00 (dd, J=5.0, 1.8 Hz, 1H), 7.68 (d,J=7.6 Hz, 1H), 7.54 (t, J=8.0 Hz, 1H), 7.17 (s, 2H), 3.66 (m, 1H), 1.08(m, 2H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-hydroxy-3,4′-bipyridine-2′-carboxamide

C₂₂H₁₈N₆O₂. 399.2 (M+1). ¹H NMR (DMSO) d 12.18 (br, 1H), 10.91 (s, 1H),8.71 (d, J=5.2 Hz, 1H), 8.63 (s, 1H), 8.58 (s, 1H), 8.32 (s, 1H), 8.14(d, 2.8 Hz, 1H), 8.05 (m, 2H), 7.92 (dd, J=5.2, 1.6 Hz, 1H), 7.68 (d,J=8.0 Hz, 1H), 7.54 (t, J=8.0 Hz, 1H), 6.50 (d, J=10.0 Hz, 1H), 3.65 (m,1H), 1.08 (m, 2H), 0.94 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1-methyl-1H-imidazol-5-yl)picolinamide

C₂₁H₁₉N₇O. 386.1 (M+1). ¹H NMR (DMSO) d 10.92 (s, 1H), 8.78 (d, J=5.2Hz, 1H), 8.62 (s, 1H), 8.57 (s, 1H), 8.26 (s, 1H), 8.07 (d, J=8.0 Hz,1H), 7.86 (m, 2H), 7.69 (d, J=8.0 Hz, 1H), 7.54 (m, 2H), 3.86 (s, 3H),3.66 (m, 1H), 1.08 (m, 2H), 0.94 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(2-methoxypyrimidin-5-yl)picolinamide

C₂₂H₁₉N₇O₂. 414.8 (M+1). ¹H NMR (DMSO) d 10.99 (s, 1H), 9.19 (s, 2H),8.84 (d, J=5.2 Hz, 1H), 8.63 (s, 1H), 8.59 (s, 1H), 8.51 (d, J=0.8 Hz,1H), 8.05-8.12 (m, 2H), 7.69 (d, J=7.6 Hz, 1H), 7.55 (t, J=8 Hz, 1H),4.01 (s, 3H), 3.64-3.68 (m, 1H), 1.06-1.11 (m, 2H), 0.92-0.97 (m, 2H).

6′-methyl-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₁H₁₈N₆O. 371.5 (M+1). ¹H NMR (DMSO) d 10.73 (s, 1H), 9.09 (d, J=2 Hz,1H), 8.71 (d, J=3.6 Hz, 1H), 8.59 (s, 1H), 8.26-8.34 (m, 3H), 8.09 (d,J=7.6 Hz, 1H), 7.99 (s, 1H), 7.50-7.61 (m, 3H), 3.80 (s, 3H), 2.73 (s,3H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-fluoro-5-methyl-3,4′-bipyridine-2′-carboxamide

C₂₃H₁₉FN₆O. 415.3 (M+1). ¹H NMR (DMSO) d 10.95 (s, 1H), 8.85 (d, J=5.2Hz, 1H), 8.58-8.64 (m, 3H), 8.43-8.49 (m, 2H), 8.05-8.10 (m, 2H), 7.70(d, J=8.4 Hz, 1H), 7.55 (t, J=8.4 Hz, 1H), 3.65-3.70 (m, 1H), 2.36 (s,3H), 1.06-1.12 (m, 2H), 0.92-0.97 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(2,4-dimethoxypyrimidin-5-yl)picolinamide

C₂₃H₂₁N₇O₃. 444.2 (M+1). ¹H NMR (DMSO) d 10.92 (s, 1H), 8.80 (d, J=4.8Hz, 1H), 8.67 (s, 1H), 8.62 (s, 1H), 8.57 (s, 1H), 8.38-8.40 (m, 1H),8.06 (d, J=8 Hz, 1H), 7.91 (dd, J=1.6, 4.8 Hz, 1H), 7.68 (d, J=8 Hz,1H), 7.54 (d, J=8 Hz, 1H), 4.02 (s, 3H), 3.99 (s, 3H), 3.62-3.70 (m,1H), 1.05-1.11 (m, 2H), 0.90-0.96 (m, 2H).

6-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₅H₂₂N₆O. 423.1 (M+1). ¹H NMR (DMSO) d 10.94 (s, 1H), 8.93 (d,J=2.0 Hz,1H), 8.82 (d, J=2.8 Hz, 1H), 8.63 (s, 1H), 8.58 (s, 1H), 8.43 (d, J=1.2Hz, 1H), 8.19 (dd, J=8.0, 2.8 Hz, 1H), 8.06 (m, 2H), 7.68 (d, 8.0 Hz,1H), 7.55 (t, J=8.0 Hz, 1H), 7.49 (d, J=8.0 Hz, 1H), 3.66 (m, 1H), 2.21(m, 1H), 1.02 (m, 8H).

N2′-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′,6-dicarboxamide

C₂₃H₁₉N₇O₂. 426.1 (M+1). ¹H NMR (DMSO) d 10.98 (s, 1H), 9.14 (d, J=1.6Hz, 1H), 8.90 (d, J=4.8 Hz, 1H), 8.63 (s, 1H), 8.60 (s, 1H), 8.53 (t,J=2.4 Hz, 1H), 8.51 (d, J=2.4 Hz, 1H), 8.17 (m, 3H), 8.08 (d, J=8.0 Hz,1H), 7.77 (s, 1H), 7.70 (d, J=8.0 Hz, 1H), 7.56 (t, J=8.0 Hz, 1H), 3.67(m, 1H), 1.08 (m 2H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(trifluormethyl)-3,4′-bipyridine-2′-carboxamide

C₂₃H₁₇F₃N₆O. 451.1 (M+1). ¹H NMR (DMSO) d 10.99 (s, 1H), 9.31 (d, J=1.2Hz, 1H), 8.93 (d, J=4.8 Hz, 1H), 8.64 (s, 1H), 8.63 (s, 1H), 8.60 (s,1H), 8.56 (d, J=1.2 Hz, 1H), 8.18 (dd, J=5.2, 2.0 Hz, 1H), 8.09 (m, 2H),7.70 (d, J=8.0 Hz, 1H), 7.56 (t, J=8.0 Hz, 1H), 3.67 (m, 1H), 1.08 (m,2H), 0.95 (m, 2H). ¹⁹F NMR (DMSO) d −66.4.

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-methyl-3,4′-bipyridine-2′-carboxamide

C₂₃H₂₀N₆O. 397.1 (M+1). ¹H NMR (DMSO) d 10.94 (s, 1H), 8.99 (d, J=2.0Hz, 1H), 8.84 (d, J=5.2 Hz, 1H), 8.63 (s, 1H), 8.59 (s, 1H), 8.46 (d,J=0.8 Hz, 1H), 8.24 (dd, J=8.0, 2.4 Hz, 1H), 8.08 (m, 2H), 7.69 (d,J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 7.46 (d, J 8.0 Hz, 1H), 3.67 (m,1H), 2.56 (s, 3H), 1.08 (m, 2H), 0.95 (m, 2H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide

C₂₁H₁₇N₇O. 384.1 (M+1). ¹H NMR (DMSO) d 10.70 (s, 1H), 9.19 (d, J=2 Hz,1H), 8.88 (d, J 5 Hz, 1H), 8.74 (dd, J=2.5 Hz, 1H), 8.70 (s, 1H), 8.55(d, J=1 Hz, 1H), 8.40 (d, J=8 Hz, 1H), 8.35-8.40 (m, 1H), 8.15 (dd, J=2,5 Hz, 1H), 8.11 (t, J=8 Hz, 1H), 7.87-7.91 (m, 1H), 7.62 (dd, J=5, 8 Hz,1H), 4.11-4.20 (m, 1H), 0.98-1.10 (m, 4H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(2,2,2-trifluoroethoxy)-3,4′-bipyridine-2′-carboxamide

C₂₄H₁₉F₃N₆O₂. 481.1 (M+1). ¹H NMR (DMSO) d 10.94 (s, 1H), 8.83 (d, J=4.4Hz, 1H), 8.79 (d, J=2.4 Hz, 1H), 8.63 (s, 1H), 8.59 (s, 1H), 8.45 (d,J=1.2 Hz, 1H), 8.38 (dd, J=8.8, 2.8 Hz, 1H), 8.07 (m, 2H), 7.69 (d,J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 7.19 (d, J=8.0 Hz, 1H), 5.10 (q,J=9.0 Hz, 2H), 3.66 (m, 1H), 1.08 (m, 2H), 0.95 (m, 2H). ¹⁹F NMR (DMSO)d −72.28 (t, J=9.0 Hz, 3F).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-methyl-3,4′-bipyridine-2′-carboxamide

C₂₃H₂₀N₆O×HCO₂H. 397.1 (M+1). ¹H NMR (DMSO) d 10.97 (s, 1H), 8.86 (d,J=5.2 Hz, 1H), 8.62 (s, 1H), 8.57 (s, 1H), 8.54 (d, J=5.2 Hz, 1H), 8.50(s, 1H), 8.16 (d, J=1.2 Hz, 1H), 8.14 (s, 1H), 8.07 (dd, J=8.0, 0.8 Hz,1H), 7.80 (dd, J=5.2, 2.0 Hz, 1H), 7.69 (d, J=8.0 Hz, 1H), 7.55 (t,J=8.0 Hz, 1H), 7.43 (d, J=5.2 Hz, 1H), 3.66 (m, 1H), 2.33 (s, 3H), 1.08(m, 2H), 0.94 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5-(trifluoromethyl)-3,4′-bipyridine-2′-carboxamide

C₂₃H₁₇F₃N₆O. 451.1 (M+1). ¹H NMR (DMSO) d 10.98 (s, 1H), 9.40-9.42 (m,1H), 9.11-9.13 (m, 1H), 8.90 (d, J=5 Hz, 1H), 8.75-8.78 (m, 1H), 8.63(s, 1H), 8.58-8.62 (m, 2H), 8.21 (dd, J=2.6 Hz, 1H), 8.05-8.10 (m, 1H),7.70 (d, J=8 Hz, 1H), 7.56 (t, J=8 Hz, 1H), 3.63-3.68 (m, 1H), 1.05-1.10(m, 2H), 0.94-0.98 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5-fluoro-3,4′-bipyridine-2′-carboxamide

C₂₂H₁₇FN₆O. 400.4 (M+1). ¹H NMR (DMSO) d 10.96 (s, 1H), 9.02 (m, 1H),8.88 (d, J=5 Hz, 1H), 8.74 (d, J=3 Hz, 1H), 8.63 (s, 1H), 8.59 (s, 1H),8.51-8.54 (m, 1H), 8.36-8.41 (m, 1H), 8.14 (dd, J=2.6 Hz, 1H), 8.07 (d,J=9 Hz, 1H), 7.69 (d, J=8 Hz, 1H), 7.55 (t, J=8 Hz, 1H), 3.62-3.68 (m,1H), 1.06-1.12 (m, 2H), 0.94-0.97 (m, 2H).

N2′-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′,5-dicarboxamide

C₂₃H₁₉N₇O₂. 426.1 (M+1). ¹H NMR (DMSO) d 10.97 (s, 1H), 9.25 (d, J=2 Hz,1H), 9.14 (d, J=2 Hz, 1H), 8.89 (d, J=5 Hz, 1H), 8.72 (t, J=2 Hz, 1H),8.63 (s, 1H), 8.58-8.63 (m, 2H), 8.37-8.39 (m, 1H), 8.18 (dd, J=2.5 Hz,1H), 8.06-8.10 (m, 1H), 7.74-7.76 (m, 1H), 7.70 (d, J=8 Hz, 1H), 7.56(t, J=8 Hz, 1H), 3.65-3.70 (m, 1H), 1.08-1.12 (m, 2H), 0.93-0.97 (m,2H).

5-cyano-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₃H₁₇N₇O. 407.4 (M+1). ¹H NMR (DMSO) d 10.97 (s, 1H), 9.40 (d, J=2 Hz,1H), 9.16 (d, J=2 Hz, 1H), 8.95 (t, J=2 Hz, 1H), 8.91 (d, J=5 Hz, 1H),8.63 (s, 1H), 8.57-8.61 (m, 2H), 8.18 (dd, J=2.5 Hz, 1H), 8.05-8.09 (m,1H), 7.70 (d, J=7 Hz, 1H), 7.56 (t, J=8 Hz, 1H), 3.65-3.69 (m, 1H),1.05-1.11 (m, 2H), 0.94-0.98 (m, 2H).

2-amino-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₂H₁₉N₇O. 398.1 (M+1). ¹H NMR (DMSO) d 10.93 (s, 1H), 8.79 (d, J=5.2Hz, 1H), 8.62 (s, 1H), 8.58 (s, 1H), 8.24 (s, 1H), 8.05 (m, 2H), 7.76(dd, J=5.2, 1.2 Hz, 1H), 7.68 (d, J=7.2 Hz, 1H), 7.53 (m, 2H), 6.73 (m,1H), 6.03 (br, 2H), 3.67 (m, 1H), 1.08 (m, 2H), 0.94 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-2-methoxy-3,4′-bipyridine-2′-carboxamide

C₂₃H₂₀N₆O₂. 413.1 (M+1). ¹H NMR (DMSO) d 10.93 (s, 1H), 8.82 (d, J=5.2Hz, 1H), 8.62 (s, 1H), 8.56 (s, 1H), 8.38 (s, 1H), 8.32 (dd, J=5.2, 2.0Hz, 1H), 8.07 (d, J=7.2 Hz, 1H), 8.01 (dd, J=7.2, 1.6 Hz, 1H), 7.91 (dd,J=5.2, 2.0 Hz, 1H), 7.69 (d, J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 7.20(dd, J=7.2, 5.2 Hz, 1H), 3.95 (s, 3H), 3.67 (m, 1H), 1.08 (m, 2H), 0.95(m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1-methyl-1H-pyrazol-4-yl)picolinamide

C₂₁H₁₉N₇O. 386.1 (M+1). ¹H NMR (DMSO) d 10.85 (s, 1H), 8.67 (d, J=5.2Hz, 1H), 8.62 (s, 1H), 8.58 (s, 1H), 8.56 (s, 1H), 8.29 (d, J=1.2 Hz,1H), 8.18 (s, 1H), 8.04 (d, J=9.2 Hz, 1H), 7.85 (dd, J=5.2, 1.6 Hz, 1H),7.68 (d, J=8.0 Hz, 1H), 7.54 (t, J=8.0 Hz, 1H), 3.91 (s, 3H), 3.66 (m,1H), 1.08 (m, 2H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(imidazo[1,2-a]pyridin-3-yl)picolinamide

C₂₄H₁₉N₇O. 422.1 (M+1). ¹H NMR (DMSO) d 10.96 (s, 1H), 8.85 (m, 2H),8.63 (s, 1H), 8.59 (s, 1H), 8.41 (d, J=1.2 Hz, 1H), 8.20 (s, 1H), 8.09(d, J=8.0 Hz, 1H), 8.04 (dd, J=5.2, 1.6 Hz, 1H), 7.76 (d, J=9.2 Hz, 1H),7.70 (d, J=8.0 Hz, 1H), 7.56 (t, J=8.0 Hz, 1H), 7.45 (dt, J=6.8, 1.2 Hz,1H), 7.12 (dt, J=7.2, 1.2 Hz, 1H), 3.67 (m, 1H), 1.08 (m, 2H), 0.95 (m,2H).

6-Chloro-[3,2′;5′,4″]terpyridine-2″-carboxylic acid[3-(4-cyclopropyl-4H-[1,2,4]triazol-3-yl)-phenyl]amide

C₂₇H₂₀ClN₇O. 494.0 (M+1). ¹H NMR (DMSO) d 10.97 (s, 1H), 9.26 (d, J=2Hz, 1H), 9.22 (d, J=2 Hz, 1H), 8.89 (d, J=5 Hz, 1H), 8.63 (s, 1H),8.58-8.62 (m, 2H), 8.55-8.56 (m, 1H), 8.52 (dd, J=2, 8 Hz, 1H), 8.30 (d,J=8 Hz, 1H), 8.18 (dd, J=2, 8 Hz, 1H), 8.09 (d, J=8 Hz, 1H), 7.70 (d,J=8 Hz, 1H), 7.56 (t, J=8 Hz, 1H), 3.65-3.69 (m, 1H), 1.06-1.11 (m, 2H),0.94-0.98 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5-methoxy-3,4′-bipyridine-2′-carboxamide

C₂₃H₂₀N₆O₂. 413.1 (M+1). ¹H NMR (DMSO) d 10.96 (s, 1H), 8.86 (d, J=5 Hz,1H), 8.68 (d, J=2 Hz, 1H), 8.63 (s, 1H), 8.58-8.60 (m, 1H), 8.49-8.51(m, 1H), 8.44 (d, J=2 Hz, 1H), 8.11 (dd, J=2.5 Hz, 1H), 8.08 (d, J=5 Hz,1H), 7.88 (t, J=8 Hz, 1H), 7.69 (t, J=8 Hz, 1H), 7.55 (t, J=8 Hz, 1H),3.96 (s, 3H), 3.65-3.68 (m, 1H), 1.06-1.12 (m, 2H), 0.92-0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1,2-dimethyl-1H-imidazol-5-yl)picolinamide

C₂₂H₂₁N₇O. 400.1 (M+1). ¹H NMR (DMSO) d 10.91 (s, 1H), 8.76 (d, J=5.2,1H), 8.62 (s, 1H), 8.56 (s, 1H), 8.18 (d, J=0.8 Hz, 1H), 8.07 (d, J=8.0Hz, 1H), 7.77 (dd, J=5.2, 1.6 Hz, 1H), 7.68 (d, J=8.0 Hz, 1H), 7.54 (t,J=8.0 Hz, 1H), 7.33 (s, 1H), 3.69 (s, 3H), 3.66 (m, 1H), 2.40 (s, 3H),1.08 (m, 2H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-2-methyl-3,4′-bipyridine-2′-carboxamide

C₂₃H₂₀N₆O. 397.1 (M+1). ¹H NMR (DMSO) d 10.97 (s, 1H), 8.85 (d, J=4.8Hz, 1H), 8.62 (s, 1H), 8.58 (s, 1H), 8.57 (s, 1H), 8.16 (s, 1H), 8.07(d, J=8.0 Hz, 1H), 7.80 (m, 2H), 7.69 (d, J=8.0 Hz, 1H), 7.54 (t, J=8.0Hz, 1H), 7.40 (dd, J=7.8, 1.2 Hz, 1H), 3.66 (m, 1H), 2.48 (s, 3H), 1.07(m, 2H), 0.95 (m, 2H).

N5-tert-butyl-N2′-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′,5-dicarboxamide

C₂₇H₂₇N₇O₂×HCO₂H. 482.1 (M+1). ¹H NMR (DMSO) d 10.98 (s, 1H), 9.20 (d,J=2 Hz, 1H), 9.05 (d, J=2 Hz, 1H), 8.89 (d, J=5 Hz, 1H), 8.63 (s, 1H),8.58-8.62 (m, 3H), 8.22 (s, 1H), 8.17 (dd, J=2.5 Hz, 1H), 8.08 (d, J=8Hz, 1H), 7.70 (d, J=8 Hz, 1H), 7.70 (d, J=8 Hz, 1H), 7.56 (t, J=8 Hz,1H), 3.64-3.70 (m, 1H), 1.43 (s, 9H), 1.06-1.11 (m, 2H), 0.92-0.97 (m,2H).

5-chloro-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₂H₁₇ClN₆O. 417.1 (M+1). ¹H NMR (DMSO) d 10.96 (s, 1H), 9.06 (s, 1H),8.85 (d, J=5 Hz, 1H), 8.76 (s, 1H), 8.60 (s, 1H), 8.58 (s, 1H), 8.56 (s,1H), 8.50 (d, J=2 Hz, 1H), 8.10 (d, J=5 Hz, 1H), 8.04 (d, J=9 Hz, 1H),7.66 (d, J=8 Hz, 1H), 7.52 (d, J=8 Hz, 1H), 3.65-3.68 (m, 1H), 1.06-1.12(m, 2H), 0.93-0.98 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(3-(methylsulfonyl)phenyl)picolinamide

C₂₄H₂₁N₅O₃S. 460.0 (M+1). ¹H NMR (DMSO) d 10.97 (s, 1H), 8.89 (d, J=6Hz, 1H), 8.63 (s, 1H), 8.60 (s, 1H), 8.54 (s, 1H), 8.40 (s, 1H), 8.28(d, J=8 Hz, 1H), 8.11-8.16 (m, 1H), 8.08 (d, J=8 Hz, 2H), 7.86 (t, J=8Hz, 1H), 7.70 (d, J=8 Hz, 1H), 7.56 (t, J=8 Hz, 1H), 3.64-3.70 (m, 1H),3.35 (s, 3H), 1.06-1.12 (m, 2H), 0.92-0.97 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(2-(methylsulfonyl)-phenyl)picolinamide

C₂₄H₂₁N₅O₃S. 460.1 (M+1). ¹H NMR (DMSO) d 10.97 (s, 1H), 8.82 (d, J=4Hz, 1H), 8.62 (s, 1H), 8.55-8.57 (m, 1H), 8.13-8.17 (m, 2H), 8.04-8.08(m, 1H), 7.74-7.88 (m, 3H), 7.69 (d, J=8 Hz, 1H), 7.55 (t, J=8 Hz, 1H),7.50 (dd, J=2, 8 Hz, 1H), 3.63-3.67 (m, 1H), 3.07 (s, 3H), 1.06-1.09 (m,2H), 0.92-0.96 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(methylsulfonyl)phenyl)picolinamide

C₂₄H₂₁N₅O₃S. 460.1 (M+1). ¹H NMR (DMSO) d 10.97 (s, 1H), 8.89 (d, J=5Hz, 1H), 8.61 (d, J=5 Hz, 1H), 8.61 (d, J=13 Hz, 1H), 8.49 (d, J=1 Hz,1H), 8.19 (d, J=8 Hz, 2H), 8.05-8.14 (m, 4H), 7.70 (d, J=8 Hz, 1H), 7.56(t, J=8 Hz, 1H), 3.64-3.69 (m, 1H), 3.30 (s, 3H), 1.06-1.12 (m, 2H),0.92-0.97 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(pyridin-3-yl)quinoline-2-carboxamide

C₂₆H₂₀N₆O. 433.1 (M+1). ¹H NMR (DMSO) d 11.04 (s, 1H), 8.84 (d, J=2 Hz,1H), 8.80 (dd, J=1, 5 Hz, 1H), 8.64 (s, 1H), 8.62 (s, 1H), 8.40 (d, J=8Hz, 1H), 8.18 (s, 1H), 8.11 (d, J=8 Hz, 2H), 8.00 (t, J=7 Hz, 1H), 7.93(d, J=8 Hz, 1H), 7.79 (t, J=8 Hz, 1H), 7.73 (d, J=8 Hz, 1H), 7.67 (dd,J=6, 8 Hz, 1H), 7.59 (t, J=8 Hz, 1H), 3.65-3.70 (m, 1H), 1.06-1.12 (m,2H), 0.93-0.98 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(quinolin-3-yl)picolinamide

C₂₆H₂₀N₆O. 423.1 (M+1). ¹H NMR (DMSO) d 10.99 (s, 1H), 9.44 (d, J=2.0Hz, 1H), 9.02 (s, 1H), 8.92 (d, J=5.2 Hz, 1H), 8.66 (s, 1H), 8.63 (s,1H), 8.62 (s, 1H), 8.28 (d, J=4.0 Hz, 1H), 8.18 (d, J=8.0 Hz, 1H), 8.11(m, 2H), 7.87 (t, J=7.2 Hz, 1H), 7.72 (m, 2H), 7.56 (t, J=8.0 Hz, 1H),3.68 (m, 1H), 1.08 (m, 2H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(isoquinolin-4-yl)picolinamide

C₂₆H₂₀N₆O. 433.1 (M+1). ¹H NMR (DMSO) d 11.03 (s, 1H), 9.47 (s, 1H),8.95 (d, 5.2 Hz, 1H), 8.62 (s, 1H), 8.59 (m, 2H), 8.30 (m, 2H), 8.09 (d,J=12.0 Hz, 1H), 7.94 (d, J=5.2 Hz, 1H), 7.91 (m, 2H), 7.81 (m, 1H), 7.70(d, J=8.0 Hz, 1H), 7.56 (t, J=8.0 Hz, 1H), 3.67 (m, 1H), 1.08 (m, 2H),0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1,5-dimethyl-1H-pyrazol-4-yl)picolinamide

C₂₂H₂₁N₇O. 400.1 (M+1). ¹H NMR (DMSO) d 10.87 (s, 1H), 8.70 (d, J=5.2Hz, 1H), 8.62 (s, 1H), 8.56 (s, 1H), 8.18 (d, J=1.2 Hz, 1H), 8.05 (d,J=9.2 Hz, 1H), 7.92 (s, 1H), 7.73 (dd, J=5.2, 2.0 Hz, 1H), 7.67 (d,J=8.0 Hz, 1H), 7.54 (t, J=8.0 Hz, 1H), 3.83 (s, 3H), 3.66 (m, 1H), 2.50(s, 3H), 1.07 (m, 2H), 0.94 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(dimethylamino)-3,4′-bipyridine-2′-carboxamide

C₂₄H₂₃N₇O. 426.1 (M+1). ¹H NMR (DMSO) d 10.89 (s, 1H), 8.70 (m, 2H),8.62 (s, 1H), 8.58 (s, 1H), 8.36 (d, J=1.2 Hz, 1H), 8.07 (m, 2H), 8.96(dd, J=5.6, 2.0 Hz, 1H), 7.68 (d, J=8.0 Hz, 1H), 7.54 (t, J=8.0 Hz, 1H),6.79 (d, J=8.8 Hz, 1H), 3.66 (m, 1H), 3.12 (s, 6H), 1.08 (m, 2H), 0.95(m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1H-pyrrolo[2,3-b]pyridin-5-yl)picolinamide

C₂₄H₁₉N₇O. 422.1 (M+1). ¹H NMR (DMSO) d 11.91 (s, 1H), 10.94 (s, 1H),8.81 (d, J=5.2 Hz, 1H), 7.50 (d, J=2.0, 1H), 8.63 (s, 1H), 8.60 (s, 1H),8.52 (m, 2H), 8.10 (m, 2H), 7.69 (d, J=8.0 Hz, 1H), 7.58 (m, 2H), 6.59(dd, J=8.0, 4.0 Hz, 1H). 3.67 (m, 1H), 1.09 (m, 2H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-fluoro-3,4′-bipyridine-2′-carboxamide

C₂₂H₁₇FN₆O. 422.1 (M+1). ¹H NMR (DMSO) d 10.96 (s, 1H), 8.86 (d, J=4.8Hz, 1H), 8.82 (d, J=2.4 Hz, 1H), 8.63 (s, 1H), 8.57 (m, 2H), 8.48 (d,J=1.2 Hz, 1H), 8.09 (m, 2H), 7.69 (d, J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz,1H), 7.40 (dd, J=8.4, 2.8 Hz, 1H), 3.66 (m, 1H), 1.08 (m, 2H), 0.96 (m,2H). ¹⁹F NMR (DMSO) d −68.2 (d, J=8.0 Hz, 1F).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(N-cyclopropylsulfamoyl)-phenyl)picolinamide

C₂₆H₂₄N₆O₃S. 500.6 (M+1). ¹H NMR (DMSO) d 10.97 (s, 1H), 8.88 (d, J=5Hz, 1H), 8.63 (s, 1H), 8.60 (s, 1H), 8.40 (s, 1H), 8.16 (d, J=8 Hz, 1H),8.05-8.12 (m, 3H), 7.98 (d, J=8 Hz, 2H), 7.69 (d, J=8 Hz, 2H), 7.55 (t,J=8 Hz, 1H), 3.63-3.68 (m, 1H), 2.12-2.20 (m, 1H), 1.06-1.10 (m, 2H),0.93-0.97 (m, 2H), 0.50-0.54 (m, 2H), 0.40-0.44 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-sulfamoylphenyl)picolinamide

C₂₃H₂₀N₆O₃S. 461.0 (M+1). ¹H NMR (DMSO) d 10.96 (s, 1H), 8.87 (d, J=5Hz, 1H), 8.63 (s, 1H), 8.60 (s, 1H), 8.48 (d, J=1 Hz, 1H), 8.12 (d, J=8Hz, 2H), 8.09 (dd, J=2.5 Hz, 1H), 8.07 (s, 1H), 7.99 (d, J=8 Hz, 2H),7.70 (d, J=8 Hz, 1H), 7.55 (t, J=8 Hz, 1H), 7.51 (s, 2H), 3.63-3.68 (m,1H), 1.06-1.12 (m, 2H), 0.92-0.97 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(N-methylsulfamoyl)-phenyl)picolinamide

C₂₄H₂₂N₆O₃S. 475.0 (M+1). ¹H NMR (DMSO) d 10.97 (s, 1H), 8.88 (d, J=5Hz, 1H), 8.63 (s, 1H), 8.60 (s, 1H), 8.49 (s, 1H), 8.15 (d, J=8 Hz, 2H),8.09 (dt, J=2.5 Hz, 1H), 7.95 (d, J=8 Hz, 2H), 7.69 (d, J=8 Hz, 1H),7.61 (q, J=8 Hz, 1H), 7.56 (t, 18 Hz, 1H), 3.64-3.69 (m, 1H), 2.46 (s,3H), 1.06-1.12 (m, 2H), 0.92-0.97 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(N-isopropylsulfamoyl)-phenyl)picolinamide

C₂₄H₂₂N₆O₃S. 503.1 (M+1). ¹H NMR (DMSO) d 10.96 (s, 1H), 8.87 (d, J=5Hz, 1H), 8.63 (s, 1H), 8.60 (s, 1H), 8.48 (s, 1H), 8.13 (d, J=8 Hz, 2H),8.06-8.10 (m, 2H), 7.97 (d, J=8 Hz, 2H), 7.74 (d, J=7 Hz, 1H), 7.69 (d,J=8 Hz, 1H), 7.55 (t, J=8 Hz, 1H), 3.65-3.68 (m, 1H), 3.28 (m, 1H),0.94-1.10 (m, 10H).

6-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide

C₂₄H₂₁N₇O. 424.1 (M+1). ¹H NMR (DMSO) d 10.67 (s, 1H), 8.94 (d, J=2 Hz,1H), 8.83 (d, J=8 Hz, 1H), 8.69 (s, 1H), 8.49 (d, J=1 Hz, 1H), 8.39 (d,J=8 Hz, 2H), 8.20 (dd, J=2, 8 Hz, 1H), 8.07-8.11 (m, 2H), 7.88 (d, J=7Hz, 1H), 7.49 (d, J=8 Hz, 1H), 4.08-4.12 (m, 1H), 2.18-2.24 (m, 1H),0.98-1.10 (m, 8H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4-(methylsulfonyl)-phenyl)picolinamide

C₂₃H₂₀N₆O₃S. 461.1 (M+1). ¹H NMR (DMSO) d 10.70 (s, 1H), 8.90 (d, J=5Hz, 1H), 8.69 (s, 1H), 8.54 (d, J=1 Hz, 1H), 8.41 (d, J=8 Hz, 1H), 8.21(d, J=8 Hz, 2H), 8.09-8.17 (m, 4H), 7.89 (d, J=8 Hz, 1H), 4.09-4.13 (m,1H), 3.30 (s, 3H), 0.98-1.08 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(ethylsulfonyl)phenyl)picolinamide

C₂₅H₂₃N₅O₃S. 474.1 (M−1). ¹H NMR (DMSO) d 10.97 (s, 1H), 8.89 (d, J=5Hz, 1H), 8.61 (d, J=13 Hz, 2H), 8.50 (s, 1H), 8.20 (d, J=8 Hz, 2H), 8.11(d, J=4 Hz, 1H), 8.04-8.10 (m, 3H), 7.70 (d, J=8 Hz, 1H), 7.56 (t, J=8Hz, 1H), 3.64-3.68 (m, 1H), 3.38 (q, J=7 Hz, 2H), 1.15 (t, J=7 Hz, 3H),1.06-1.10 (m, 2H), 0.93-0.98 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(isopropylsulfonyl)phenyl)picolinamide

C₂₆H₂₅N₅O₃S. 488.0 (M+1). ¹H NMR (DMSO) d 10.97 (s, 1H), 8.89 (d, J=5Hz, 1H), 8.61 (d, J=12 Hz, 2H), 8.50 (s, 1H), 8.20 (d, J=8 Hz, 2H), 8.12(d, J=5 Hz, 1H), 8.08 (d, J=8 Hz, 1H), 8.03 (d, J=8 Hz, 2H), 7.70 (d,J=8 Hz, 1H), 7.55 (t, J=8 Hz, 1H), 3.65-3.69 (m, 1H), 3.52 (sept, J=7Hz, 1H), 1.19 (d, J=7 Hz, 6H), 1.04-1.10 (m, 2H), 0.93-0.98 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1-methyl-2-phenyl-1H-imidazol-5-yl)picolinamide

C₂₇H₂₃N₇O. 462.1 (M+1). ¹H NMR (DMSO) d 10.94 (s, 1H), 8.82 (d, J=4.8Hz, 1H), 8.63 (s, 1H), 8.58 (s, 1H), 8.32 (d, J=1.2 Hz, 1H), 8.08 (d,J=8.0 Hz, 1H), 7.89 (dd, J=5.2, 2.0 Hz, 1H), 7.78 (m, 2H), 7.69 (d,J=8.0 Hz, 1H), 7.61 (s, 1H), 7.54 (m, 4H), 3.82 (s, 3H), 3.67 (m, 1H),1.08 (m, 2H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6′-(trifluoromethyl)-3,4′-bipyridine-2′-carboxamide

C₂₃H₁₇F₃N₆O. 451.1 (M+1). ¹H NMR (DMSO) d 10.72 (s, 1H), 9.22 (s, 1H),8.76 (d, J=4 Hz, 1H), 8.70 (d, J=1 Hz, 1H), 8.63 (s, 1H), 8.58 (d, J=1Hz, 1H), 8.52 (s, 1H), 8.46 (dt, J=2, 8 Hz, 1H), 7.99-8.15 (m, 1H), 7.74(d, J=8 Hz, 1H), 7.56-7.76 (m, 2H), 3.64-3.68 (m, 1H), 1.05-1.09 (m, 2H)0.94-0.98 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(quinolin-3-yl)-6-(trifluoromethyl)picolinamide

C₂₇H₁₉F₃N₆O. 501.0 (M+1). ¹H NMR (DMSO) d 10.75 (s, 1H), 9.53 (d, J=2Hz, 1H), 9.15 (d, J=2 Hz, 1H), 8.88 (s, 1H), 8.74 (d, J=1 Hz, 1H), 8.64(s, 1H), 8.55 (s, 1H), 8.15 (dd, J=8.15 Hz, 2H), 8.03 (d, J=10 Hz, 1H),7.86-7.92 (m, 1H), 7.70-7.76 (m, 2H), 7.59 (t, J=8 Hz, 1H), 3.63-3.68(m, 1H), 1.07-1.12 (m, 2H) 0.94-0.98 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1H-pyrrolo[3,2-b]pyridin-6-yl)picolinamide

C₂₄H₁₉N₇O. 422.1 (M+1). ¹H NMR (DMSO) d 11.70 (s, 1H), 10.95 (s, 1H),8.89 (d, J=2.0 Hz, 1H), 8.82 (d, J=4.4 Hz, 1H), 8.64 (s, 1H), 8.61 (s,1H), 8.51 (d, J=1.2 Hz, 1H), 8.33 (s, 1H), 8.13 (dd, J=4.4, 1.6 Hz, 1H),8.08 (d, J=8.0 Hz, 1H), 7.85 (t, J=2.8 Hz, 1H), 7.69 (d, J=8.0 Hz, 1H),7.56 (t, J=8.0 Hz, 1H), 6.68 (s, 1H), 3.67 (m, 1H), 1.08 (m, 2H), 0.95(m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-cyclopropylphenyl)picolinamide

C₂₆H₂₃N₅O. 422.1 (M+1). ¹H NMR (DMSO) d 10.92 (s, 1H), 8.78 (d, J=5.2Hz, 1H), 8.63 (s, 1H), 8.59 (s, 1H), 8.39 (d, J=1.2 Hz, 1H), 8.07 (d,J=8.0 Hz, 1H), 7.99 (dd, J=5.2, 1.2 Hz, 1H), 7.79 (d, J=8.0 Hz, 2H),7.69 (d, J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 7.27 (d, J=8.0 Hz, 2H),3.66 (m, 1H), 2.01 (m, 1H), 1.08 (m, 2H), 1.05 (m, 2H), 0.95 (m, 2H),0.76 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(furo[3,2-b]pyridin-6-yl)picolinamide

C₂₄H₁₈N₆O₂. 423.1 (M+1). ¹H NMR (DMSO) d 11.01 (s, 1H), 9.09 (s, 1H),8.87 (m, 2H), 8.68 (s, 1H), 8.64 (s, 1H), 8.57 (s, 1H), 8.47 (s, 1H),8.18 (m, 1H), 8.11 (m, 1H), 7.70 (d, J=8.0 Hz, 1H), 7.59 (t, J=8.0 Hz,1H), 7.26 (s, 1H), 3.71 (m, 1H), 1.11 (m, 2H), 0.99 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(3-methyl-3H-imidazo[4,5-b]pyridin-6-yl)picolinamide

C₂₄H₂₀N₈O. 437.1 (M+1). ¹H NMR (DMSO) d 10.96 (s, 1H), 8.92 (s, 1H),8.84 (d, J=5.2 Hz, 1H), 8.60 (m, 5H), 8.15 (d, J=5.2 Hz, 1H), 8.09 (d,J=8.0 Hz, 1H), 7.70 (d, J=8.0 Hz, 1H), 7.56 (t, J=8.0 Hz, 1H), 3.91 (s,3H), 3.68 (m, 1H), 1.09 (m, 2H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(6-cyclopropylpyridin-3-yl)pyrimidine-4-carboxamide

C₂₄H₂₁N₇O. 424.1 (M+1). ¹H NMR (DMSO) d 11.10 (s, 1H), 9.47 (d, J=1.6Hz, 1H), 9.31 (d, J=1.6 Hz, 1H), 8.65 (d, J=1.6 Hz, 1H), 8.63 (s, 1H),8.57 (s, 1H), 8.54 (dd, J=8.0, 2.0 Hz, 1H), 8.07 (d, J=8.0 Hz, 1H), 7.72(d, J=8.0 Hz, 1H), 7.58 (d, J=8.0 Hz, 1H), 7.53 (t, J=8.0 Hz, 1H), 3.66(m, 1H), 2.24 (m, 1H), 1.05 (m, 6H), 0.96 (m, 2H).

6-cyclopropoxy-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₅H₂₂N₆O₂. 439.1 (M+1). ¹H NMR (DMSO) d 10.93 (s, 1H), 8.81 (d, 5.2 Hz,1H), 8.78 (d, J=2.4 Hz, 1H), 8.63 (s, 1H), 8.58 (s, 1H), 8.43 (d, J=0.8Hz, 1H), 8.30 (dd, J=8.4, 2.4 Hz, 1H), 8.04 (m, 2H), 7.69 (d, J=8.0 Hz,1H), 7.55 (t, J=8.0 Hz, 1H), 7.05 (d, J=8.0 Hz, 1H), 4.30 (m, 1H), 3.67(m, 1H), 1.08 (m, 2H), 0.95 (m, 2H), 0.81 (m, 2H), 0.74 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(2-oxoimidazolidin-1-yl)phenyl)picolinamide

C₂₆H₂₃N₇O₂×HCl. 466.1 (M+1). ¹H NMR (DMSO) d 11.03 (s, 1H), 9.28 (s,1H), 8.77 (d, S=5.2 Hz, 1H), 8.68 (s, 1H), 8.43 (d, J=1.2 Hz, 1H), 8.14(d, J=8.0 Hz, 1H), 8.02 (dd, J=5.2, 2.0 Hz, 1H), 7.90 (d, J=8.8, 2H),7.76 (d, J=8.8 Hz, 2H), 7.72 (d, J=8.0, 1H), 7.62 (t, J=8.0 Hz, 1H),7.12 (b, 1H), 3.93 (t, J=8.0 Hz, 2H), 3.79 (m, 1H), 3.45 (t, J=8.0 Hz,2H), 1.06 (m, 2H), 0.95 (m, 2H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4-(N-methylsulfamoyl)phenyl)picolinamide

C₂₃H₂₁N₇O₃S. 476.2 (M+1). ¹H NMR (DMSO) d 10.74 (s, 1H), 9.00 (s, 1H),8.89 (d, J=5 Hz, 1H), 8.54 (d, J=1 Hz, 1H), 8.44 (d, J=8 Hz, 1H),8.12-8.19 (m, 4H), 7.90-7.97 (m, 3H), 7.64 (d, J=8 Hz, 2H), 4.14-4.18(m, 1H), 2.46 (s, 3H), 1.04-1.12 (m, 4H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(quinolin-3-yl)picolinamide

C₂₅H₁₉N₇O. 434.1 (M+1). ¹H NMR (DMSO) d 10.73 (s, 1H), 9.44 (s, 1H),9.03 (s, 1H), 8.92 (d, J=5 Hz, 1H), 8.70 (d, J=7 Hz, 2H), 8.42 (d, J=8Hz, 1H), 8.31 (d, J=4 Hz, 1H), 8.17 (d, J=8 Hz, 1H), 8.12 (t, J=8 Hz,2H), 7.85-7.91 (m, 2H), 7.72 (t, J=8 Hz, 1H), 4.09-4.13 (m, 1H),0.97-1.11 (m, 4H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(quinolin-3-yl)benzamide

C₂₆H₂₀N₆O. 433.1 (M+1). ¹H NMR (DMSO) d 10.94 (s, 1H), 9.38 (d, J=2 Hz,1H), 8.79 (d, J=2 Hz, 1H), 8.65 (s, 1H), 8.47 (s, 1H), 8.31 (d, J=8 Hz,1H), 8.16 (d, J=8 Hz, 1H), 8.02-8.10 (m, 4H), 7.77-7.83 (m, 2H), 7.74(t, J=8 Hz, 1H), 7.68 (t, J=8 Hz, 1H), 4.24-4.28 (m, 1H), 0.92-1.02 (m,4H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(6-cyclopropylpyridin-3-yl)benzamide

C₂₅H₂₂N₆O. 423.1 (M+1). ¹H NMR (DMSO) d 10.87 (s, 1H), 8.82 (d, J=2 Hz,1H), 8.65 (s, 1H), 8.28 (d, J=8 Hz, 1H), 8.25 (s, 1H), 8.05 (d, J=8 Hz,1H), 8.04 (t, J=8 Hz, 1H), 7.95 (t, J=7 Hz, 2H), 7.81 (d, J=8 Hz, 1H),7.65 (t, J=8 Hz, 1H), 7.42 (d, J=8 Hz, 1H), 4.22-4.27 (m, 1H), 2.14-2.19(m, 1H), 0.91-1.02 (m, 8H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(pyridin-3-yl)benzamide

C₂₂H₁₈N₆O. 383.1 (M+1). ¹H NMR (DMSO) d 10.90 (s, 1H), 9.02 (d, J=2 Hz,1H), 8.65 (s, 1H), 8.62 (dd, J=1, 4 Hz, 1H), 8.30 (d, J=2 Hz, 1H), 8.28(s, 1H), 8.21 (dt, J=2, 8 Hz, 1H), 8.05 (t, J=8 Hz, 1H), 8.00 (d, J=8Hz, 2H), 7.81 (d, J=7 Hz, 1H), 7.69 (t, J=8 Hz, 1H), 7.54 (dd, J=5, 8Hz, 1H), 4.25 (dddd, J=4, 8, 12, 16 Hz, 1H), 0.90-1.02 (m, 4H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(5-cyclopropylpyrazin-2-yl)picolinamide

C₂₄H₂₁N₇O. 422.1 (M+1). ¹H NMR (DMSO) d 10.95 (s, 9.31 (d, J=0.8 Hz,1H), 8.89 (d, J=4.4 Hz, 1H), 8.83 (d, J=1.2 Hz, 2H), 8.63 (s, 1H), 8.60(s, 1H), 8.386 (dd, J=5.2, 1.6 Hz, 1H), 8.07 (d, J=8.0 Hz, 1H), 7.67 (d,J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 3.66 (m, 1H), 2.35 (m, 1H), 1.10(m, 6H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)-4-fluorophenyl)-6-ethyl-3,4′-bipyridine-2′-carboxamide

C₂₄H₂₁FN₆O. 429.2 (M+1). ¹H NMR (DMSO) d 11.02 (s, 1H), 9.00 (d, J=2 Hz,1H), 8.83 (d, J=5 Hz, 1H), 8.70 (s, 1H), 8.44 (s, 1H), 8.22-8.28 (m,2H), 8.14-8.19 (m, 1H), 8.08 (dd. J=2.5 Hz, 1H), 7.47 (t, J=9 Hz, 2H),3.40-3.45 (m, 1H), 2.84 (q, J=8 Hz, 2H), 1.28 (t, J=8 Hz, 3H), 0.81-0.93(m, 4H).

6-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)-2-fluorophenyl)-3,4′-bipyridine-2′-carboxamide

C₂₅H₂₁FN₆O. 441.1 (M+1). ¹H NMR (DMSO) d 10.63 (s, 1H), 8.94 (d, J=2 Hz,1H), 8.82 (d, J=9 Hz, 1H), 8.72 (s, 1H), 8.45 (s, 1H), 8.25-8.30 (m,1H), 8.20 (dd, J=2, 8 Hz, 1H), 8.08 (dd, J=2.5 Hz, 1H), 7.24-7.50 (m,3H), 3.43-3.47 (m, 1H), 2.18-2.24 (m, 1H), 1.00-1.07 (m, 4H), 0.82-0.93(m, 4H).

5-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₅H₂₂N₆O. 423.1 (M+1). ¹H NMR (DMSO) d 10.94 (s, 1H), 8.84 (m, 2H),8.63 (s, 1H), 8.59 (s, 1H), 8.54 (d, J=2.0 Hz, 1H), 8.47 (d, J=0.8 Hz,1H), 8.08 (m, 2H), 7.90 (t, J=2.0 Hz, 1H), 7.69 (d, J=8.0 Hz, 1H), 7.55(t, J=8.0 Hz, 1H), 3.66 (m, 1H), 2.07 (m, 1H), 1.06 (m, 4H), 0.96 (m,4H).

6-cyclopropyl-N-(2-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-4-yl)-3,4′-bipyridine-2′-carboxamide

C₂₄H₂₁N₇O. 424.2 (M+1). ¹H NMR (DMSO) d 11.31 (s, 1H), 8.94 (d, J=2 Hz,1H), 8.84 (d, J=5 Hz, 1H), 8.77 (d, J=5 Hz, 1H), 8.66 (t, J=2 Hz, 2H),8.45 (d, J=2 Hz, 1H), 8.20 (dd, J=2, 8 Hz, 1H), 8.09 (dd, J=2.5 Hz, 1H),8.06 (dd, J=2, 6 Hz, 1H), 7.50 (d, J=8 Hz, 1H), 3.98-4.02 (m, 1H),2.07-2.21 (m, 1H), 0.93-1.05 (m, 8H).

N-(2-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-4-yl)-4-(quinolin-3-yl)picolinamide

C₂₅H₁₉N₇O. 434.1 (M+1). ¹H NMR (DMSO) d 11.36 (s, 1H), 9.44 (d, J=2 Hz,1H), 9.02 (d, J=2 Hz, 1H), 8.94 (d, J=13 Hz, 1H), 8.78 (d, J==2 Hz, 1H),8.68 (s, 1H), 8.67 (s, 2H), 8.31 (dd, J=2.5 Hz, 1H), 8.18 (d, J=8 Hz,1H), 8.12 (d, J=8 Hz, 1H), 8.09 (dd, J=2, 6 Hz, 1H), 7.84-7.89 (m, 1H),7.72 (t, J=8 Hz, 1H), 3.97-4.04 (m, 1H), 0.93-1.04 (m, 4H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)-2-fluorophenyl)-3,4′-bipyridine-2′-carboxamide

C₂₂H₁₇FN₆O. 401.1 (M+1). ¹H NMR (DMSO) d 10.63 (s, 1H), 9.12 (d, J=2 Hz,1H), 8.87 (d, J=5 Hz, 1H), 8.71-8.74 (m, 2H), 8.50 (d, J=1 Hz, 1H),8.32-8.36 (m, 1H), 8.25-8.29 (m, 1H), 8.14 (dd, J=2.5 Hz, 1H), 7.58-7.62(m, 1H), 7.42-7.49 (m, 2H), 3.43-3.47 (m, 1H), 0.82-0.93 (m, 4H).

N-(4-(4-cyclopropyl-4H-1,2,4-triazol-3-ylpyridin-2-yl)-3,4′-bipyridine-2′-carboxamide

C₂₁H₁₇N₇O. 384.2 (M+1). ¹H NMR (DMSO) d 10.64 (s, 1H), 9.13 (d, J=2 Hz,1H), 9.02 (s, 1H), 8.89 (d, J=5 Hz, 1H), 8.76 (s, 1H), 8.71-8.74 (m,1H), 8.59 (d, J=6 Hz, 1H), 8.54 (s, 1H), 8.33-8.37 (m, 1H), 8.17 (dd,J=2.5 Hz, 1H), 7.83 (dd, J=1, 5 Hz, 1H), 7.60 (dd, J=5, 8 Hz, 1H),3.73-3.77 (m, 1H), 1.04-1.21 (m, 4H).

6-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)-5-fluorophenyl)-3,4′-bipyridine-2′-carboxamide

C₂₅H₂₁FN₆O. 441.2 (M+1). ¹H NMR (DMSO) d 11.17 (s, 1H), 8.93 (d, J=2 Hz,1H), 8.83 (d, J=5 Hz, 1H), 8.66 (s, 1H), 8.42-8.47 (m, 2H), 8.19 (dd,J=2, 8 Hz, 1H), 7.47-7.53 (m, 2H), 3.67-3.73 (m, 1H), 2.17-2.23 (m, 1H),0.95-1.06 (m, 8H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)-5-fluorophenyl)-3,4′-bipyridine-2′-carboxamide

C₇₇H₁₇FN₆O. 401.1 (M+1). ¹H NMR (DMSO) d 10.20 (s, 1H), 9.12 (d, J=2 Hz,1H), 8.87 (d, J=5 Hz, 1H), 8.73 (dd, J=2.5 Hz, 1H), 8.67 (s, 1H), 8.48(d, J=5 Hz, 2H), 8.34 (d, J=8 Hz, 1H), 8.11-8.15 (m, 1H), 8.06 (d, J=8Hz, 1H), 7.60 (dd, J=2, 8 Hz, 1H), 7.52 (d, J=9 Hz, 1H), 3.69-3.72 (m,1H), 1.08-1.13 (m, 2H), 0.93-0.98 (m, 2H).

6-cyclopropyl-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide

C₂₄H₂₃N₇O. 426.3 (M+1). ¹H NMR (DMSO) d 10.70 (s, 1H), 8.95 (d, J=2 Hz,1H), 8.91 (s, 1H), 8.85 (d, J=5 Hz, 1H), 8.49 (d, J=1 Hz, 1H), 8.36 (d,J=8 Hz, 1H), 8.21 (dd, J=2, 8 Hz, 1H), 8.07-8.15 (m, 2H), 7.91 (d, J=7Hz, 1H), 7.50 (d, J=8.0 Hz, 1H), 5.53 (sept, J=6 Hz, 1H), 2.18-2.24 (m,1H), 1.51 (d, J=6 Hz, 6H) 0.98-1.06 (m, 4H).

(S)-6-cyclopropyl-N-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide

C₂₄H₂₀F₃N₇O×HCl. 480.1 (M+1). ¹H NMR (DMSO) d 11.10 (s, 1H), 9.17 (s,1H), 9.04 (s, 1H), 8.89 (d, J=9 Hz, 1H), 8.52 (s, 1H), 8.40 (br s, 1H),8.30 (d, J=8 Hz, 1H), 8.08-8.14 (m, 2H), 7.99 (d, J=8 Hz, 1H), 7.59 (d,J=8 Hz, 1H), 7.06 (app p, J=7 Hz, 1H), 6.00 (br s, 1H), 2.30-2.34 (m,1H), 1.85 (d, J=7 Hz, 3H), 1.08-1.15 (m, 4H).

5-(2,5-difluorophenyl)-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)nicotinamide

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)benzamide

C₂₅H₄N₆O₂×HCl. 441.1 (M+1). ¹H NMR (DMSO) d 11.18 (s, 1H), 9.32 (s, 1H),9.10 (d, J=1.6 Hz, 1H), 8.94 (d, J=8.0 Hz, 1H), 8.48 (s, 1H), 8.35 (d,J=8.0 Hz, 1H), 8.22 (d, J=8.0 Hz, 1H), 8.10 (m, 3H), 7.88 (d, J=8.0 Hz,1H), 7.75 (t, J=8.0 Hz, 1H), 4.43 (m, 1H), 1.65 (s, 6H), 1.05 (m, 4H).

6-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5′-methyl-3,4′-bipyridine-2′-carboxamide

C₂₅H₂₃N₇O. 438.6 (M+1). ¹H NMR (DMSO) d 10.62 (s, 1H), 8.72 (s, 1H),8.69 (s, 1H), 8.55 (s, 1H), 8.37 (d, J=8 Hz, 1H). 8.09 (t, J=8 Hz, 1H),8.04 (s, 1H), 7.87 (d, J=8 Hz, 1H), 7.84 (dd, J=2, 8 Hz, 1H), 7.47 (d,J=8 Hz, 1H), 4.07-4.11 (m, 1H), 2.39 (s, 3H) 2.18-2.22 (m, 1H),0.98-1.07 (m, 8H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-(6-cyclopropylpyridin-3-yl)-2-fluorobenzamide

C₂₅H₂₁FN₆O. 441.2 (M+1). ¹H NMR (DMSO) d 10.98 (s, 1H), 8.76 (d, 2 Hz,1H), 8.64 (s, 1H), 8.29 (d, J=9 Hz, 1H), 8.05 (t, J=8 Hz, 1H), 8.01 (d,J=2 Hz, 1H), 7.98-8.00 (m, 1H), 7.88-7.94 (m, 1H), 7.86 (d, J=8 Hz, 1H),7.48 (t, J=8 Hz, 1H), 7.40 (d, J=8 Hz, 1H), 4.18-4.22 (m, 1H), 2.17-2.20(m, 1H), 0.91-1.07 (m, 8H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(6-cyclopropylpyridin-3-yl)quinoline-2-carboxamide

C₂₈H₂₃N₇O. 474.4 (M+1). ¹H NMR (DMSO) d 10.83 (s, 1H), 8.68 (s, 1H),8.62 (d, J=1 Hz, 1H), 8.39 (d, J=9 Hz, 1H), 8.32 (d, J=8 Hz, 1H), 8.17(s, 1H), 8.10 (t, J=8 Hz, 1H), 7.91-797 (m, 3H), 7.88 (d, J=8 Hz, 1H),7.77 (t, J=8 Hz, 1H), 7.54 (d, J=8 Hz, 1H), 4.07-4.10 (m, 1H), 2.21-2.24(m, 1H), 1.01-1.10 (m, 8H).

6-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-6′-methyl-3,4′-bipyridine-2′-carboxamide

C₂₅H₂₃N₇O. 438.2 (M+1). ¹H NMR (DMSO) d 10.65 (s, 1H), 9.91 (s, 1H),8.69 (s, 1H), 8.38 (d, J=8 Hz, 1H), 8.29 (s, 1H), 8.17 (d, J=8 Hz, 1H),8.10 (t, J=8 Hz, 1H), 7.98 (s, 1H), 7.88 (d, J=8 Hz, 1H), 7.47 (d, J=8Hz, 1H), 3.96-4.00 (m, 1H), 2.68 (s, 3H), 2.18-2.22 (m, 1H), 1.00-1.11(m, 8H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(6-cyclopropylpyridin-3-yl)-7,8-dimethylquinoline-2-carboxamide

C₃₀H₂₇N₇O. 502.3 (M+1). ¹H NMR (DMSO) d 10.83 (s, 1H), 8.71 (s, 1H),8.61 (s, 1H), 8.40 (d, J=9 Hz, 1H), 8.08-8.14 (m, 2H), 7.90-7.95 (m,2H), 7.69 (d, J=8 Hz, 1H), 7.61 (d, J=9 Hz, 1H), 7.55 (d, J=8 Hz, 1H),4.09-4.14 (m, 1H), 2.84 (s, 3H), 2.55 (s, 3H), 2.11-2.15 (m, 1H),1.03-1.15 (m, 8H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(6-cyclopropylpyridin-3-yl)-7,8-dimethylquinoline-2-carboxamide

C₃₀H₂₇N₇O. 502.3 (M+1). ¹H NMR (DMSO) d 10.83 (s, 1H), 8.71 (s, 1H),8.61 (s, 1H), 8.40 (d, J=9 Hz, 1H), 8.08-8.14 (m, 2H), 7.90-7.95 (m,2H), 7.69 (d, J=8 Hz, 1H), 7.61 (d, J=9 Hz, 1H), 7.55 (d, J=8 Hz, 1H),4.09-4.14 (m, 1H), 2.84 (s, 3H), 2.55 (s, 3H), 2.11-2.15 (m, 1H),1.03-1.15 (m, 8H).

3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-fluorobenzamide

C₂₃H₂₀FN₇O. 430.2 (M+1). ¹H NMR (MeOH) d 9.62 (s, 1H), 9.52 (d, J=1 Hz,1H), 8.50 (d, J=8 Hz, 1H), 8.23 (s, 1H), 8.15 (t, J=8 Hz, 1H), 7.90-8.01(m, 3H), 7.88 (d, J=9 Hz, 1H), 4.42-4.45 (m, 1H), 2.04-2.09 (m, 1H),1.23-1.27 (m, 2H), 1.14-1.19 (m, 4H) 0.91-0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1,5-naphthyridin-3-yl)picolinamide

C₂₅H₁₉N₇O. 434.1 (M+1). ¹H NMR (DMSO) d 11.14 (s, 1H), 9.56 (d, J=2.4Hz, 1H), 9.16 (d, J=1.6 Hz, 1H), 9.14 (d, J=1.6 Hz, 1H), 8.99 (d, J=1.2Hz, 1H), 8.95 (d, J=5.2 Hz, 1H), 8.73 (s, 1H), 8.69 (d, J=1.2 Hz, 1H),8.59 (d, J=8.0 Hz, 1H), 8.35 (dd, J=5.2, 2.0 Hz, 1H), 8.19 (d, J=8.0 Hz,1H), 7.92 (dd, J=8.4, 4.4 Hz, 1H), 2.75 (d, J=8.0 Hz, 1H), 2.66 (t,J=8.0 Hz, 1H), 3.84 (m, 1H), 1.15 (m, 4H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(1,5-naphthyridin-3-yl)benzamide

C₂₅H₁₉N₇O. 434.1 (M+1). ¹H NMR (DMSO) d 11.01 (s, 1H), 9.51 (d, J=2.4Hz, 1H), 9.09 (dd, J=4.4, 1.6 Hz, 1H), 8.86 (s, 1H), 8.86 (s, 1H), 8.54(m, 2H), 8.32 (d, J=8.0 Hz, 1H), 8.24 (d, J=8.0 Hz, 1H), 8.07 (m, 2H),7.83 (m, 2H), 7.77 (t, J=8.0 Hz, 1H), 4.27 (m, 1H), 1.00 (m, 4H).

6-cyclopropyl-N-(4-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide

C₂₄H₂₁N₇O. 424.2 (M+1). ¹H NMR (DMSO) d 10.65 (s, 1H), 8.97-9.02 (m,1H), 8.91-8.95 (m, 1H), 8.83 (d, J=5 Hz, 1H), 8.75 (s, 1H), 8.57 (d, J=8Hz, 1H), 8.49 (s, 1H), 8.18-8.22 (m, 1H), 8.09 (s, 1H), 7.77-7.81 (m,1H), 7.49 (d, J=8 Hz, 1H), 3.73-3.76 (m, 1H), 2.17-2.21 (m, 1H),1.00-1.19 (m, 8H).

6-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)-4-fluorophenyl)-3,4′-bipyridine-2′-carboxamide

C₂₅H₂₁FN₆O. 441.3 (M+1). ¹H NMR (DMSO) d 11.01 (s, 1H), 8.92 (d, J=1 Hz,1H), 8.81 (d, J=5 Hz, 1H), 8.70 (s, 1H), 8.42 (d, J=1 Hz, 1H), 8.27 (dd,J=2, 6 Hz, 1H), 8.13-8.19 (m, 2H), 8.05 (dd, J=2.5 Hz, 1H), 7.44-7.50(m, 2H), 3.40-3.44 (m, 1H), 2.17-2.23 (m, 1H), 0.81-1.06 (m, 8H).

6-tert-butyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3-carboxamide

C₂₆H₂₆N₆O. 439.1 (M+1). ¹H NMR (DMSO) d 10.94 (s, 1H), 9.04 (d, J=1.6Hz, 1H), 8.85 (d, J=5.2 Hz, 1H), 8.63 (s, 1H), 8.58 (s, 1H), 8.46 (d,J=1.2 Hz, 1H), 8.28 (dd, J=8.4, 2.4 Hz, 1H), 8.08 (m, 2H), 7.69 (d,J=8.0 Hz, 1H), 7.62 (d, J=8.0 Hz, 1H), 7.55 (d, J=8.0 Hz, 1H), 3.67 (m,1H), 1.37 (s, 9H), 1.08 (m, 2H), 0.95 (m, 2H).

6-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6′-methyl-3,4′-bipyridine-2′-carboxamide

C₂₆H₂₄N₆O. 437.2 (M+1). ¹H NMR (DMSO) d 10.69 (s, 1H), 8.90 (s, 1H),8.63 (s, 1H), 8.55 (s, 1H), 8.23 (s, 1H), 8.15 (dd, J=2, 8 Hz, 1H), 8.03(d, J=8 Hz, 1H), 7.93 (s, 1H), 7.70 (d, J=8 Hz, 1H), 7.56 (t, J=8.0 Hz,1H), 7.47 (d, J=8 Hz, 1H), 3.65-3.69 (m, 1H), 2.71 (s, 3H), 2.19-2.22(m, 1H), 0.94-1.10 (m, 8H).

6-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5′-methyl-3,4′-bipyridine-2′-carboxamide

C₂₆H₂₄N₆O. 437.2 (M+1). ¹H NMR (DMSO) d 10.89 (s, 1H), 8.71 (s, 1H),8.62 (s, 1H), 8.57 (s, 1H), 8.54 (d, J=2 Hz, 1H), 8.06 (d, J=8 Hz, 1H),7.99 (s, 1H), 7.83 (dd, J=2, 8 Hz, 1H), 7.67 (d, J=8 Hz, 1H), 7.53 (t,J=8.0 Hz, 1H), 7.46 (d, J=8 Hz, 1H), 3.63-3.67 (m, 1H), 2.39 (s, 3H),2.18-2.22 (m, 1H), 0.91-1.08 (m, 8H).

6′-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2,3′-bipyridine-6-carboxamide

C₂₄H₂₁N₇O. 424.3 (M+1). ¹H NMR (DMSO) d 10.83 (s, 1H), 9.23 (d, J=2 Hz,1H), 8.70 (s, 1H), 8.44 (dd, J=2, 8 Hz, 1H), 8.33 (t, J=5 Hz, 2H),8.18-8.24 (m, 2H), 8.13 (t, J=8 Hz, 1H), 7.92 (d, J=8 Hz, 1H), 7.47 (d,J=8 Hz, 1H), 4.10-4.14 (m, 1H), 2.19-2.23 (m, 1H), 0.99-1.11 (m, 8H).

6′-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2,3′-bipyridine-5-carboxamide

C₂₄H₂₁N₇O×HCOOH. 424.2 (M+1). ¹H NMR (DMSO) d 11.05 (s, 1H), 9.12 (d,J=2 Hz, 1H), 9.08 (d, J=2 Hz, 1H), 8.66 (s, 1H), 8.60 (t, J=2 Hz, 1H),8.29 (d, J=8 Hz, 1H), 8.19 (br s, 1H), 8.12 (dd, J=2, 8 Hz, 1H), 8.07(t, J=8 Hz, 1H), 7.83 (d, J=7 Hz, 1H), 7.46 (d, J=8 Hz, 1H), 4.20-4.24(m, 1H), 2.17-2.21 (m, 1H), 0.90-1.03 (m, 8H).

6′-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2,3′-bipyridine-4-carboxamide

C₂₄H₂₁N₇O. 424.2 (M+1). ¹H NMR (DMSO) d 11.10 (s, 1H), 9.18 (d, J=2 Hz,1H), 8.87 (d, J=5 Hz, 1H), 8.66 (s, 1H), 8.44 (s, 1H), 8.38 (dd, J=2, 8Hz, 1H), 8.29 (d, J=8 Hz, 1H), 8.08 (t, J=8 Hz, 1H), 7.85 (d, J=7 Hz,1H), 7.81 (dd, J=1, 5 Hz, 1H), 7.45 (d, J=8 Hz, 1H), 4.19-4.24 (m, 1H),2.15-2.21 (m, 1H), 0.90-1.04 (m, 8H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-(6-cyclopropylpyridin-3-yl)-2,4-difluorobenzamide

C₂₅H₂₀F₂N₆O. 459.3 (M+1). ¹H NMR (DMSO) d 10.98 (s, 1H), 8.65 (s, 1H),8.62 (s, 1H), 8.26 (d, J=8 Hz, 1H), 8.05 (t, J=8 Hz, 1H), 7.95 (t, J=8Hz, 1H), 7.84-7.90 (m, 2H), 7.63 (t, J=10 Hz, 1H), 7.44 (t, J=8 Hz, 1H),4.16-4.20 (m, 1H), 2.15-2.19 (m, 1H), 0.93-1.01 (m, 8H).

6′-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-2,3′-bipyridine-4-carboxamide

C₂₅H₂₂N₆O. 423.3 (M+1). ¹H NMR (DMSO) d 10.72 (s, 1H), 9.18 (d, J=2 Hz,1H), 8.88 (d, J=5 Hz, 1H), 8.63 (s, 1H), 8.43 (d, J=9 Hz, 2H), 8.38 (dd,J=2, 8 Hz, 1H), 7.94 (d, J=8 Hz, 1H), 7.83 (dd, J=1, 9 Hz, 1H), 7.74 (d,J=8 Hz, 1H), 7.56 (t, J=8 Hz, 1H), 7.46 (d, J=8 Hz, 1H), 3.62-3.66 (m,1H), 2.16-2.21 (m, 1H), 0.93-1.01 (m, 8H).

6′-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-2,3′-bipyridine-6-carboxamide

C₂₅H₂₂N₆O. 423.3 (M+1). ¹H NMR (DMSO) d 10.72 (s, 1H), 9.42 (d, J=2 Hz,1H), 8.64 (s, 1H), 8.62 (dd, J=2, 8 Hz, 1H), 8.52 (s, 1H), 8.28 (dd,J=1, 7 Hz, 1H), 8.11-8.18 (m, 2H), 8.04 (d, J=8 Hz, 1H), 7.72 (d, J=8Hz, 1H), 7.58 (d, J=8 Hz, 1H), 7.48 (d, J=8 Hz, 1H), 3.64-3.68 (m, 1H),2.18-2.22 (m, 1H), 0.93-1.08 (m, 8H):

4-chloro-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-(6-cyclopropylpyridin-3-yl)-2-fluorobenzamide

C₂₅H₂₀ClFN₆O. 475.2 (M+1). ¹H NMR (DMSO) d 11.01 (s, 1H), 8.65 (s, 1H),8.50 (d, J=2 Hz, 1H), 8.25 (d, J=8 Hz, 1H), 8.04 (t, J=8 Hz, 1H),7.76-7.85 (m, 4H), 7.42 (d, J=8 Hz, 1H), 4.14-4.18 (m, 1H), 2.15-2.19(m, 1H), 0.92-1.02 (m, 8H).

4-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide

C₂₂H₁₉N₇OS. 430.1 (M+1). ¹H NMR (DMSO) d 11.02 (s, 1H), 8.92 (d, J=4.8,1H), 8.65 (s, 1H), 8.59 (s, 1H), 8.54 (d, J=1.2 Hz, 1H), 8.17 (dd,J=5.2, 2.0 Hz, 1H), 8.07 (d, J=8.0 Hz, 1H), 7.70 (d, J=8.0 Hz, 1H), 7.55(t, J=8.0 Hz, 1H), 3.67 (m, 1H), 2.67 (m, 1H), 1.33 (m, 2H), 1.15 (m,2H), 1.08 (m, 2H), 0.95 (m, 2H).

C. Similarly, following the procedures as described in Examples 1-13where appropriate, other compounds of formula (I) are prepared.

EXAMPLE 14 Preparation of Compounds of Formula I via N-arylation ofHalorarenes A. Preparation of a Compound of Formula (I) in which X². X³,X⁴, X⁶, X⁷ and X⁸ are (CR4), X¹ and X⁵ are N, R¹ is Cyclopropyl. R² isHydrogen, and R³ is 4-Imidazol-1-yl A. Preparation ofN-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1H-imidazol-1-1)picolinamide

A suspension of4-bromo-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide(35 mg, 0.091 mmol), imidazole (8 mg, 0.117 mmol), cupric oxide (1 mg,0.007 mmol), 4,7-dimethoxy-1,10-phenanthroline (3 mg, 0.012 mmol (or8-hydroxyquinoline may be used as the ligand with comparable results),cesium carbonate (41 mg, 0.126 mmol), and PEG-3350 (20 mg) inbutyronitrile (1 mL) was heated at 120° C. for 16 hours. The solvent wasremoved under reduced pressure and the residue purified by reverse-phaseHPLC to giveN-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1H-imidazol-1-yl)picolinamideas a white powder (14 mg, 0.377 mmol, 41% yield).

C₂₀H₁₇N₇O. 372.3 (M+1). ¹H NMR (DMSO) d 10.98 (s, 1H), 8.83 (d, J=5.6Hz, 1H), 8.72 (s, 1H), 8.64 (s, 1H), 8.58 (s, 1H), 8.44 (d, J=2.4 Hz,1H), 8.15 (s, 1H), 8.07 (m, 2H), 7.70 (d, J=8.0 Hz, 1H), 7.55 (t, J=8.0Hz, 1H), 7.21 (s, 1H), 3.66 (m, 1H), 1.08 (m, 2H), 0.95 (m, 2H).

B. Similarly, following the procedure of Example 14, optionallyreplacing4-bromo-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamidewith other compounds of formula (5), and optionally replacing imidazolewith other amines, the following compounds of Formula I were prepared:

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1H-1,2,4-triazol-1-yl)picolinamide

C₁₉H₁₆N₈O. 373.6 (M+1). ¹H NMR (DMSO) d 11.02 (s, 1H), 9.74 (s, 1H),8.91 (d, J=9.2 Hz, 1H), 8.65 (m, 2H), 8.59 (s, 1H), 8.41 (s, 1H), 8.21(dd, J=5.6, 2.0 Hz, 1H), 8.07 (d, J=8.8 Hz, 1H), 7.70 (d, J=8.0 Hz, 1H),7.56 (t, J=8.0 Hz, 1H), 3.67 (m, 1H), 1.08 (m, 2H), 0.95 (m, 2H).

4-(1H-benzo[d]imidazol-1-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide

C₂₄H₁₉N₇O. 422.0 (M+1). ¹H NMR (DMSO) d 11.03 (s, 1H), 8.95 (d, J=5.6Hz, 1H), 8.91 (s, 1H), 8.63 (s, 1H), 8.60 (s, 1H), 8.48 (d, J=1.6 Hz,1H), 8.12 (m, 2H), 7.89 (d, J=7.6 Hz, 1H), 7.84 (d, J=7.6 Hz, 1H), 7.71(d, 8.0 Hz, 1H), 7.56 (t, 8.0 Hz, 1H), 7.42 (m, 2H), 3.67 (m, 1H), 1.08(m, 2H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-phenyl-1H-imidazol-1-yl)picolinamide

C₂₆H₂₁N₇O. 448.6 (M+1). ¹H NMR (DMSO) d 10.97 (s, 1H), 8.86 (d, J=5.6Hz, 1H), 8.80 (d, J=1.6 Hz, 1H), 8.71 (d, J=1.6 Hz, 1H), 8.63 (s, 1H),8.60 (s, 1H), 8.53 (d, J=2.0 Hz, 1H), 8.12 (dd, J=5.6, 2.4 Hz, 1H), 8.08(d, J=8.0 Hz, 1H), 7.93 (d, J=7.6 Hz, 2H), 7.71 (d, J=7.6 Hz, 1H), 7.56(t, J=8.0 Hz, 1H), 7.43 (t, J=7.6 Hz, 2H), 7.29 (t, J=7.6 Hz, 1H), 3.67(m, 1H), 1.09 (m, 2H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(2-methyl-1H-imidazol-1-yl)picolinamide

C₂₁H₁₉N₇O. 386.1 (M+1). ¹H NMR (DMSO) d 10.99 (s, 1H), 8.88 (d, J=5.2Hz, 1H), 8.62 (s, 1H), 8.56 (s, 1H), 8.18 (d, J=2.0 Hz, 1H), 8.07 (d,J=8.0 Hz, 1H), 7.87 (dd, J=5.2, 2.0 Hz, 1H), 7.70 (d, J=8.0 Hz, 1H),7.62 (s, 1H), 7.55 (t, 8.0 Hz, 1H), 7.02 (s, 1H), 3.65 (m, 1H), 2.47 (s,3H), 1.07 (m, 2H), 0.94 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-methyl-1H-imidazol-1-yl)picolinamide

C₂₁H₁₉N₇O. 386.1 (M+1). ¹H NMR (DMSO) d 10.94 (s, 1H), 8.80 (d, J=5.2Hz, 1H), 8.63 (s, 1H), 8.58 (s, 1H), 8.57 (s, 1H), 8.36 (d, J=2.4 Hz,1H), 8.06 (d, J=8.0 Hz, 1H), 7.99 (d, J=5.6, 2.4 Hz, 1H), 7.81 (s, 1H),7.69 (d, J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H). 3.66 (m, 1H), 2.19 (s,3H), 1.08 (m, 2H), 0.94 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4,5-dimethyl-1H-imidazol-1-yl)picolinamide

C₂₂H₂₁N₇O. 400.1 (M+1). ¹H NMR (DMSO) d 10.98 (s, 1H), 8.87 (d, J=5.2Hz, 1H), 8.62 (s, 1H), 8.56 (s, 1H), 8.16 (s, 1H), 8.07 (d, J=8.8 Hz,1H), 8.00 (s, 1H), 7.82 (dd, J=5.2, 1.6 Hz, 1H), 7.70 (d, J=8.0 Hz, 1H),7.55 (t, J=8.0 Hz, 1H), 3.66 (m, 1H), 2.24 (s, 3H), 2.14 (s, 3H), 1.07(m, 2H), 0.94 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(trifluoromethyl)-1H-imidazol-1-yl)picolinamide

C₂₁H₁₆F₃N₇O. 440.4 (M+1). ¹H NMR (DMSO) d 10.98 (s, 1H), 8.89 (m, 3H),8.63 (s, 1H), 8.57 (m, 2H), 8.15 (dd, J=6.0, 2.4 Hz, 1H), 8.07 (d, J=8.0Hz, 1H), 7.71 (d, J=8.0 Hz, 1H), 7.56 (t, J=8.0 Hz, 1H), 3.66 (m, 1H),1.08 (m, 2H), 0.95 (m, 2H). ¹⁹F NMR (DMSO) d −61.55.

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1H-imidazo[4,5-b]pyridin-1-yl)picolinamide

C₂₃H₁₈N₈O. 423.1 (M+1). ¹H NMR (DMSO) d 11.03 (s, 1H), 9.21 (s, 1H),8.97 (d, J=5.2 Hz, 1H), 8.63 (s, 1H), 8.58 (m, 2H), 8.50 (d, J=2.0 Hz,1H), 8.35 (dd, J=8.0, 1.2 Hz, 1H), 8.15 (dd, J=5.2, 2.0 Hz, 1H), 8.09(d, J=8.0 Hz, 1H), 7.71 (d, J=8.0 Hz, 1H), 7.57 (t, J=8.0 Hz, 1H), 7.48(dd, J=8.0, 4.8 Hz, 1H), 3.67 (m, 1H), 1.09 (m, 2H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(3H-imidazo[4,5-b]pyridin-3-yl)picolinamide

C₂₃H₁₈N₈O. 423.1 (M+1). ¹H NMR (DMSO) d 11.00 (s, 1H), 9.33 (s, 1H),9.13 (d, J=1.6 Hz, 1H), 8.95 (d, J=5.6 Hz, 1H), 8.63 (s, 1H), 8.60 (s,1H), 8.57 (dd, J=4.8, 1.6 Hz, 1H), 8.52 (dd, J=5.6, 2.0 Hz, 1H), 8.29(dd, J=8.0, 1.2 Hz, 1H), 8.09 (d, J=8.0 Hz, 1H), 7.71 (d, J=8.0 Hz, 1H),7.56 (t, J=8.0 Hz, 1H), 7.50 (dd, J=8.0, 4.8 Hz, 1H), 3.67 (m, 1H), 1.09(m, 2H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1H-imidazo[4,5-c]pyridin-1-yl)picolinamide

C₂₃H₁₈N₈O. 423.1 (M+1). ¹H NMR (DMSO) d 11.04 (s, 1H), 9.14 (s, 1H),9.07 (s, 1H), 8.99 (d, J=4.8 Hz, 1H), 8.63 (s, 1H), 8.60 (s, 1H), 8.55(d, J=5.6 Hz, 1H), 8.50 (d, J=1.6 Hz, 1H), 8.15 (dd, J=5.2, 2.0 Hz, 1H),8.09 (dd, J=8.0, 1.2 Hz, 1H), 7.93 (dd, J=5.6, 0.8 Hz, 1H), 7.71 (d,J=8.0 Hz, 1H), 7.57 (t, J=8.0 Hz, 1H), 3.67 (m, 1H), 1.08 (m, 2H), 0.95(m, 2H).

4-(1H-benzo[d][1,2,3]triazol-1-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide

C₂₃H₁₈N₈O. 423.1 (M+1). ¹H NMR (DMSO) d 11.07 (s, 1H), 9.03 (d, J=5.6Hz, 1H), 9.69 (d, J=1.6 Hz, 1H), 8.63 (s, 1H), 8.61 (s, 1H), 8.35 (dd,J=5.2, 2.0 Hz, 1H), 8.30 (d, J=8.0 Hz, 1H), 8.23 (d, J=8.0 Hz, 1H), 8.10(d, J=9.2 Hz, 1H), 7.81 (t, J=8.0 Hz, 1H), 7.71 (d, J=8.0 Hz, 1H), 7.62(t, J=8.0 Hz, 1H), 7.57 (t, J=8.0 Hz, 1H), 3.67 (m, 1H), 1.08 (m, 2H),0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-1-yl)picolinamide

C₂₄H₂₃N₇O. 426.1 (M+1). ¹H NMR (DMSO) d 10.93 (s, 1H), 8.81 (d, J=5.2Hz, 1H), 8.59 (s, 1H), 8.53 (s, 1H), 8.16 (d, J=1.6 Hz, 1H), 8.13 (s,1H), 8.03 (d, J==8.0 Hz, 1H), 7.81 (dd, J=5.6, 2.0 Hz, 1H), 7.66 (d,J=8.0 Hz, 1H), 7.52 (t, J=8.0 Hz, 1H), 3.65 (m, 1H), 2.70 (br, 2H), 2.51(br, 2H), 1.76 (br, 4H), 1.05 (m, 2H), 0.90 (m, 2H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4-phenyl-1H-imidazol-1-yl)picolinamide

C₂₅H₂₀N₈O×HCl. 449.1 (M+1). ¹H NMR (DMSO) d 10.73 (s, 1H), 9.10 (s, 1H),8.92 (d, J=3 Hz, 1H), 8.90 (br s, 1H), 8.82 (s, 1H), 8.63 (s, 1H), 8.42(br s, 1H), 8.20 (d, J=4 Hz, 1H), 8.15 (t, J=8 Hz, 1H), 7.94 (d, J=8 Hz,3H), 7.47 (t, J=8 Hz, 2H), 7.34 (t, J=7 Hz, 1H), 4.91 (br s, 1H),4.11-4.14 (m, 1H), 1.01-1.14 (m, 4H).

4-(4-chloro-1H-imidazol-1-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide

C₂₀H₁₆ClN₇O. 406.0 (M+1). ¹H NMR (DMSO) d 10.96 (s, 1H), 8.86 (d, J=5.2Hz, 1H), 8.72 (d, J=1.6 Hz, 1H), 8.63 (s, 1H), 8.58 (s, 1H), 8.46 (d,J=2.4 Hz, 1H), 8.32 (d, J=1.6 Hz, 1H), 8.05 (m, 2H), 7.70 (d, J=8.0 Hz,1H), 7.55 (t, J=8.0 Hz, 1H), 3.66 (m, 1H), 1.08 (m, 2H), 0.95 (m, 2H).

4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide

C₂₃H₂₁N₇O. 412.1 (M+1). ¹H NMR (DMSO) d 10.93 (s, 1H), 8.79 (d, J=5.6Hz, 1H), 8.63 (s, 1H), 8.58 (s, 1H), 8.55 (s, 1H), 8.36 (s, 1H), 8.06(d, J=8.0 Hz, 1H), 7.98 (m, 1H), 7.85 (m, 1H), 7.69 (d, J=8.0 Hz, 1H),7.56 (t, J=8.0 Hz, 1H), 3.66 (m, 1H), 1.88 (m, 1H), 1.08 (m, 2H), 0.94(m, 2H), 0.85 (m, 2H), 0.73 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-ethyl-1H-imidazol-1-yl)picolinamide

C₂₂H₂₁N₇O. 400.1 (M+1). ¹H NMR (DMSO) d 10.93 (s, 1H), 8.80 (d, J=5.6Hz, 1H), 8.63 (s, 1H), 8.59 (m, 2H), 8.38 (d, J=2.4 Hz, 1H), 8.06 (d,J=9.2 Hz, 1H), 8.01 (dd, J=5.6, 2.4 Hz, 1H), 7.82 (s, 1H), 7.70 (d,J=8.0 Hz, 1H), 7.55 (t, J=8 Hz, 1H), 3.66 (m, 1H), 2.56 (q, J=7.6 Hz,2H), 1.22 (t, J=7.6 Hz, 3H), 1.07 (m, 2H), 0.95 (m, 2H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4-methyl-1H-imidazol-1-yl)picolinamide

C₂₀H₁₈N₈O. 387.1 (M+1). ¹H NMR (DMSO) d 10.66 (s, 1H), 8.81 (d, J=6 Hz,1H), 8.67 (s, 1H), 8.61 (s, 1H), 8.43 (d, J=2 Hz, 1H), 8.38 (d, J=8 Hz,1H), 8.11 (t, J=8 Hz, 1H), 8.02 (dd, J=2, 6 Hz, 1H), 7.89 (d, J=7 Hz,1H), 7.83 (s, 1H), 4.07-4.11 (m, 1H), 2.19 (s, 3H), 0.91-1.06 (m, 4H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4,5-dimethyl-1H-imidazol-1-yl)picolinamide

C₂₁H₂₀N₈O. 401.1 (M+1). ¹H NMR (DMSO) d 10.68 (s, 1H), 8.88 (d, J=5 Hz,1H), 8.69 (s, 1H), 8.37 (d, J=8 Hz, 1H), 8.22 (d, J=2 Hz, 1H), 8.11 (t,J=8 Hz, 1H), 7.89 (d, J=8 Hz, 1H), 7.86 (dd, J=2.5 Hz, 1H), 4.08-4.13(m, 1H), 2.25 (s, 3H) 2.14 (s, 3H), 0.96-1.08 (m, 4H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4-isopropyl-1H-imidazol-1-yl)picolinamide

C₂₂H₂₂N₈O. 415.1 (M+1). ¹H NMR (DMSO) d 10.69 (s, 1H), 9.00 (br s, 1H),8.87 (d, J=5 Hz, 1H), 8.70 (s, 1H), 8.53 (d, J=2 Hz, 1H), 8.38 (d, J=8Hz, 1H), 8.09-8.15 (m, 2H), 8.00 (s, 1H), 7.89 (d, J=7 Hz, 1H),4.08-4.13 (m, 1H), 2.90 (sept, J=7 Hz, 1H), 1.27 (d, J=6 Hz, 6H),0.98-1.06 (m, 4H).

4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)picolinamide

C₂₂H₂₀FN₈O. 413.1 (M+1). ¹H NMR (DMSO) d 10.67 (s, 1H), 8.80 (d, J=5 Hz,1H), 8.69 (s, 1H), 8.57 (s, 1H), 8.43 (d, J=2 Hz, 1H), 8.38 (d, J=8 Hz,1H), 8.11 (t, J=8 Hz, 1H), 8.01-8.04 (m, 1H), 7.87-7.91 (m, 2H),4.08-4.11 (m, 1H), 1.83-1.89 (m, 1H), 0.94-1.06 (m, 4H), 0.73-0.85 (m,4H).

4-(4-cyclopropyl-2-methyl-1H-imidazol-1-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide

C₂₄H₂₃N₇O×HCl. 426.1 (M+1). ¹H NMR (DMSO) d 11.12 (s, 1H), 9.11 (s, 1H),9.03 (d, J=5.2 Hz, 1H), 8.62 (s, 1H), 8.37 (d, J=1.6 Hz, 1H), 8.12 (d,J=8.0 Hz, 1H), 7.99 (dd, J=51, 2.0 Hz, 1H), 7.84 (s, 1H), 7.73 (d, J=8.0Hz, 1H), 7.61 (t, J=8.0 Hz, 1H), 3.74 (m, 1H), 2.62 (s, 3H), 2.01 (m,1H), 1.10 (m, 6H), 0.86 (m, 2H).

4-(4-cyclopropyl-2-methyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)picolinamide

C₂₃H₂₂N₈O×HCl. 427.1 (M+1). ¹H NMR (DMSO) d 10.76 (s, 1H), 9.04 (d,J=5.2 Hz, 1H), 8.98 (s, 1H), 8.43 (d, J=1.6 Hz, 1H), 8.38 (d, J=8.0 Hz,1H), 8.15 (t, J=8.0 Hz, 1H), 8.03 (dd, J=5.2, 2.0 Hz, 1H), 7.93 (d,J=8.0 Hz, 1H), 7.85 (s, 1H), 4.18 (m, 1H), 2.63 (s, 3H), 2.01 (m, 1H),1.05 (m, 6H), 0.89 (m, 2H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-1-yl)picolinamide

C₂₃H₂₂N₈O×HCl. 427.1 (M+1). ¹H NMR (DMSO) d 10.76 (br, 1H), 9.38 (s,1H), 9.06 (d, J=4.8 Hz, 1H), 8.92 (br, 1H), 8.50 (s, 1H), 8.40 (br, 1H),8.15 (t, J=8.0 Hz, 1H), 8.08 (d, J=8.0 Hz, 1H), 7.96 (br, 1H), 4.15 (m,1H), 2.67 (m, 4H), 1.83 (m, 4H), 1.10 (m, 4H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4-(trifluoromethyl)-1H-imidazol-1-yl)picolinamide

C₂₀H₁₅F₃N₈O×HCl. 441.1 (M+1). ¹H NMR (DMSO) d 10.73 (s, 1H), 8.92 (m,4H), 8.64 (d, J=2.0 Hz, 1H), 8.42 (d, J=8.0 Hz, 1H), 8.19 (dd, J=5.6,2.4 Hz, 1H), 8.15 (t, J=8.0 Hz, 1H), 7.92 (d, J=7.2 Hz, 1H), 4.16 (m,1H), 1.05 (m, 4H). ¹⁹F NMR (DMSO) d −61.59 (s, 3F).

3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide

C₂₃H₂₁N₇O. 412.1 (M+1). ¹H NMR (DMSO) d 10.86 (s, 1H), 8.65 (s, 1H),8.27 (d, J=8.0 Hz, 1H), 8.21 (s, 1H), 8.15 (s, 1H), 8.05 (t, J=8.0 Hz,1H), 7.83 (m, 3H), 7.66 (t, J=8.0 Hz, 1H), 7.60 (s, 1H), 4.24 (m, 1H),1.86 (m, 1H), 1.00 (m, 4H), 0.82 (m, 2H), 0.79 (m, 2H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-isopropyl-1H-imidazol-1-yl)benzamide

C₂₃H₂₃N₇O. 414.1 (M+1). ¹H NMR (DMSO) d 10.91 (s, 1H), 8.90 (br, 1H),8.66 (s, 1H), 8.27 (m, 2H), 8.06 (t, J=8.0 Hz, 1H), 7.97 (m, 2H), 7.82(m, 2H), 7.74 (t, J=8.0 Hz, 1H), 4.25 (m, 1H), 2.94 (sept, 6.8 Hz, 1H),1.27 (d, J=6.8 Hz, 611), 0.95 (m, 4H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-1-yl)picolinamide

C₂₄H₂₁ F₃N₈O. 495.1 (M+1). ¹H NMR (DMSO) d 10.99 (s, 1H), 8.88 (d, J=5.2Hz, 1H), 8.64 (s, 1H), 8.57 (s, 1H), 8.33 (s, 1H), 8.24 (d, J=2.0 Hz,1H), 8.07 (d, J=8.0 Hz, 1H), 8.07 (d, J=8.0 Hz, 1H), 7.90 (dd, J=5.2,2.0 Hz, 1H), 7.70 (d, J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 4.58 (br,1H), 3.66 (m, 1H), 3.07 (br, 2H), 2.80 (br, 2H), 1.08 (m, 2H), 0.94 (m,2H). ¹⁹F NMR (DMSO) d −71.5 (br, 3F).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-1-yl)picolinamide

C₂₃H₂₁F₃N₉O×HCl. 495.1 (M+1). ¹H NMR (DMSO) d 10.78 (s, 1H), 9.13 (s,1H), 8.95 (d, J=5.6 Hz, 1H), 8.55 (s, 1H), 8.42 (d, J=8 Hz, 1H), 8.32(d, J=2.0 Hz, 1H), 8.16 (t, J=8.0 Hz, 1H), 7.97 (m, 2H), 5.65 (m, 1H),4.19 (m, 1H), 3.51 (m, 1H), 3.43 (m, 1H), 3.21 (m, 1H), 3.12 (m, 1H),1.08 (m, 4H). ¹⁹F NMR (DMSO) d −69.2 (br, 3F).

3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-methylbenzamide

C₂₄H₂₃N₇O. 426.3 (M+1). ¹H NMR (DMSO) d 11.12 (s, 1H), 9.11 (br s, 1H),8.64 (s, 1H), 8.29 (d, J=8 Hz, 1H), 8.04 (t, J=8 Hz, 1H), 7.87 (d, J=8.0Hz, 1H), 7.75 (d, J=7 Hz, 1H), 7.60-7.66 (m, 2H), 7.54-7.58 (m, 1H),4.23-4.27 (m, 1H), 2.22 (s, 3H), 2.00-2.07 (m, 1H), 0.85-1.04 (m, 8H).

5-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-methylbenzamide

C₂₄H₂₃N₇O. 426.1 (M+1). ¹H NMR (DMSO) d 10.99 (s, 1H), 8.63 (s, 1H),8.43 (s, 1H), 8.31 (d, J=8 Hz, 1H), 8.04 (t, J=8 Hz, 1H), 7.86 (d, J=7Hz, 1H), 7.81 (d, J=2 Hz, 1H), 7.67 (dd, J=2, 9 Hz, 1H), 7.65 (s, 1H),7.47 (d, J=8 Hz, 1H), 4.25-4.29 (m, 1H), 2.43 (s, 3H), 1.84-1.88 (m,1H), 0.82-1.00 (m, 6H), 0.70-0.73 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(perfluoroethyl)-1H-imidazol-1-yl)picolinamide

C₂₂H₁₆F₅N₇O×HCl. 490.1 (M+1). ¹H NMR (DMSO) d 11.03 (s, 1H), 8.98 (s,1H), 8.92 (m, 3H), 8.63 (s, 1H), 8.59 (s, 1H), 8.18 (dd, J=5.2, 2.0 Hz,1H), 8.12 (d, J=8.8 Hz, 1H), 7.72 (d, J=8.0 Hz, 1H), 7.60 (t, J=8.0 Hz,1H), 3.72 (m, 1H), 1.13 (m, 2H), 1.01 (m, 2H). ¹⁹F NMR (DMSO) d −83.3(s, 3H), −111.7 (s, 2H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4-(perfluoroethyl)-1H-imidazol-1-yl)picolinamide

C₂₁H₁₅F₅N₈O×HCl. 491.1 (M+1). ¹H NMR (DMSO) d 10.71 (s, 1H), 8.94 (m,3H), 8.77 (s, 1H), 8.65 (d, J=2.4 Hz, 1H), 8.39 (d, 8.0 Hz, 1H), 8.21(dd, J=5.6, 2.4 Hz, 1H), 8.13 (t, J=8.0 Hz, 1H), 7.90 (d, J=6.8 Hz, 1H),4.13 (m, 1H), 1.02 (m, 4H). ¹⁹F NMR (DMSO) d −83.3 (s, 3H), −111.7 (s,2H).

3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-methylbenzamide

C₂₄H₂₃N₇O×HCO₂H. 426.2 (M+1). ¹H NMR (DMSO) d 10.79 (s, 1H), 8.65 (s,1H), 8.24 (d, J=8 Hz, 1H), 7.98-8.06 (m, 3H), 7.96 (s, 1H), 7.79 (d, J=7Hz, 1H), 7.60 (d, J=8 Hz, 1H), 7.34 (hr s, 1H), 6.52 (s, 1H), 4.20-4.24(m, 1H), 2.28 (s, 3H), 1.83-1.89 (m, 1H), 0.84-0.99 (m, 6H), 0.73-0.76(m, 2H).

4-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)picolinamide

C₂₁H₁₉N₉O×HCl. 414.1 (M+1). ¹H NMR (DMSO) d 10.70 (s, 1H), 9.55 (s, 1H),8.88 (m, 2H), 8.62 (d, J=1.6 Hz, 1H), 8.40 (d, J=8.8 Hz, 1H), 8.15 (m,2H), 7.91 (d, J=8.0 Hz, 1H), 4.14 (m, 1H), 2.15 (m, 1H), 1.05 (m, 6H),0.94 (m, 2H).

4-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide

C₂₂H₂₀N₈O×HCl. 413.1 (M+1). ¹H NMR (DMSO) d 11.01 (s, 1H), 9.53 (s, 1H),8.90 (s, 1H), 8.87 (d, J=5.2 Hz, 1H), 8.62 (s, 1H), 8.57 (s, 1H), 8.10(m, 2H), 7.71 (d, J=8.0 Hz, 1H), 7.59 (t, J=8.0 Hz, 1H), 3.72 (m, 1H),2.15 (m, 1H), 1.02 (m, 8H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(2,2,2-trifluoro-1-hydroxyethyl)-1H-imidazol-1-yl)picolinamide

C₂₁H₁₈F₃N₇O₂×HCl. 470.1 (M+1). ¹H NMR (DMSO) d 11.09 (m, 1H), 9.42 (m,1H), 9.01 (s, 1H), 8.88 (d, J=5.2 Hz, 1H), 8.68 (s, 1H), 8.50 (d, J=2.0Hz, 1H), 8.17 (m, 3H), 7.73 (t, J=8.0 Hz, 1H), 7.64 (t, J=8.0 Hz, 1H),5.18 (q, J=7.2 Hz, 1H), 3.80 (m, 1H), 1.01 (m, 4H). ¹⁹F NMR (DMSO) d76.48 (d, J=7.2 Hz, 3F).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4-(2,2,2-trifluoro-1-hydroxyethyl)-1H-imidazol-1-yl)picolinamide

C₂₁H₁₇F₃N₈O₂×HCl. 471.1 (M+1). ¹H NMR (DMSO) d 10.72 (s, 1H), 8.89 (m,3H), 8.55 (s, 1H), 8.41 (d, J=8.0 Hz, 1H), 8.26 (s, 1H), 8.15 (m, 2H),7.92 (d, J=8.0 Hz, 1H), 5.15 (d, J=7.2 Hz, 1H), 4.16 (m, 1H), 1.06 (m,4H). ¹⁹F NMR (DMSO) d 76.41 (d, J=7.2 Hz, 3F).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(2,2,2-trifluoro-1-hydroxyethyl)-1H-imidazol-1-yl)benzamide

C₂₂H₁₈F₃N₇O₂. 470.1 (M+1). ¹H NMR (DMSO) d 10.91 (s, 1H), 8.66 (s, 1H),8.34 (s, 1H), 8.27 (d, J=8.0 Hz, 1H), 8.23 (s, 1H), 8.06 (t, J=8.0 Hz,1H), 7.93 (m, 3H), 7.81 (d, J=8.0 Hz, 1H), 7.70 (t, J=8.0 Hz, 1H), 6.71(d, J=5.2 Hz, 1H), 5.06 (m, 1H), 4.23 (m, 1H), 0.98 (m, 2H), 0.94 (m,2H). ¹⁹F NMR (DMSO) d 76.44 (d, J=7.2 Hz, 3F).

3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-methylbenzamide

C₂₄H₂₃N₇O. 426.3 (M+1). ¹H NMR (DMSO) d 10.81 (s, 1H), 8.65 (s, 1H),8.26 (d, J=8 Hz, 1H), 8.20 (br s, 1H), 8.05 (t, J=8 Hz, 1H), 7.95 (s,1H), 7.81 (d, J=8 Hz, 1H), 7.68-7.72 (m, 2H), 7.60 (br s, 1H), 4.21-4.27(m, 1H), 2.46 (s, 3H) 1.83-1.86 (m, 1H), 0.89-0.98 (m, 8H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4,5-dimethyl-1H-imidazol-1-yl)benzamide

C₂₂H₂₁N₇O×HCl. 400.1 (M+1). ¹H NMR (DMSO) d 11.11 (s, 1H), 9.42 (s, 1H),9.10 (s, 1H), 8.30 (d, J=8.0 Hz, 1H), 8.24 (m, 2H), 8.10 (t, J=8.0 Hz,1H), 7.86 (m, 3H), 4.37 (m, 1H), 2.34 (s, 3H), 2.18 (s, 3H), 1.01 (m,4H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-1-yl)benzamide

C₂₄H₂₃N₇O×HCl. 426.1 (M+1). ¹H NMR (DMSO) d 11.11 (s, 1H), 9.50 (s, 1H),9.11 (s, 1H), 8.30 (m, 2H), 8.20 (d, J=8.0 Hz, 1H), 8.10 (t, J=8.0 Hz,1H), 7.87 (m, 3H), 4.39 (m, 1H), 2.71 (m, 2H), 2.61 (m, 2H), 1.83 (4H),1.01 (m, 4H).

1-(3-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-ylcarbamoyl)phenyl)-5-methyl-1H-imidazole-4-carboxylicacid

C₂₂H₁₉N₇O₃×HCl. 430.1 (M+1). ¹H NMR (DMSO) d 11.05 (s, 1H), 9.35 (s,1H), 9.13 (s, 1H), 8.29 (d, J=8.0 Hz, 1H), 8.19 (m, 2H), 8.09 (t, J=8.0Hz, 1H), 7.87 (d, 7.2 Hz, 1H), 7.82 (d, J=8.0 Hz, 1H), 7.73 (t, J=8.0Hz, 1H), 4.38 (m, 1H), 2.59 (s, 3H), 1.03 (m, 4H).

4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)quinoline-2-carboxamide

C₂₆H₂₂N₈O. 463.3 (M+1). ¹H NMR (DMSO) d 10.85 (s, 1H), 8.71 (s, 1H),8.40 (t, J=8 Hz, 2H), 8.22 (s, 1H), 8.14 (t, J=8 Hz, 1H), 8.12 (s, 1H),8.02-8.08 (m, 2H), 7.85-7.92 (m, 2H), 7.60 (s, 1H), 4.10-4.14 (m, 1H),1.93-1.97 (m, 1H), 1.05-1.12 (m, 4H), 0.80-0.90 (m, 4H).

4-chloro-3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide

C₂₃H₂₀ClN₇O. 446.2 (M+1). ¹H NMR (DMSO) d 10.92 (s, 1H), 8.66 (s, 1H),8.24 (d, J=8 Hz, 1H), 8.13 (s, 1H), 8.03-8.07 (m, 3H), 7.92 (br s, 1H),7.87 (d, J=8 Hz, 1H), 7.81 (d, J=7 Hz, 1H), 7.34 (br s, 1H), 4.18-4.21(m, 1H), 1.87-1.90 (m, 1H), 0.72-1.00 (m, 8H).

3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-methoxybenzamide

C₂₄H₂₃N₇O₂. 442.3 (M+1). ¹H NMR (DMSO) d 10.71 (s, 1H), 8.66 (s, 1H),8.25 (d, J=8 Hz, 1H), 8.00-8.11 (m, 4H), 7.78 (d, J=6 Hz, 1H), 7.40 (d,J=9 Hz, 1H), 7.40 (br s, 1H), 4.20-4.23 (m, 1H), 3.93 (s, 3H), 1.86-1.89(m, 1H), 0.70-1.00 (m, 8H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-isopropyl-1H-imidazol-1-yl)picolinamide

C₂₃H₂₃N₇O. 414.1 (M+1). ¹H NMR (DMSO) d 10.93 (s, 1H), 8.79 (d, J=5.6Hz, 1H), 8.63 (s, 1H), 8.60 (s, 1H), 8.58 (s, 1H), 8.40 (d, J=2.4 Hz,1H), 8.06 (d, J=8.8 Hz, 1H), 8.02 (dd, J=5.6, 2.4 Hz, 1H), 7.81 (s, 1H),7.70 (d, J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 3.66 (m, 1H), 2.84(sept, J=7.2 Hz, 1H), 1.24 (d, J=7.2 Hz, 6H), 1.08 (m, 2H), 0.95 (m,2H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(5-methyl-4-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-1-yl)picolinamide

C₂₄H₂₂F₃N₉O×HCl. 510.1 (M+1). ¹H NMR (DMSO) d 10.69 (s, 1H), 8.90 (d,J=5.6 Hz, 1H), 8.69 (s, 1H), 8.36 (m, 3H), 8.12 (t, J=8.0 Hz, 1H), 7.98(dd, J=5.2, 2.4 Hz, 1H), 7.89 (d, J=8.0 Hz, 1H), 4.30 (q, J=8.4 Hz, 1H),4.11 (m, 1H), 3.10 (m, 4H), 2.56 (s, 3H), 1.04 (m, 2H), 0.99 (m, 2H).¹⁹F NMR (DMSO) d −70.54 (d, J=8.8 Hz, 3F).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(5-methyl-4-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-1-yl)picolinamide

C₂₅H₂₃F₃N₈O×HCl. 509.1 (M+1). ¹H NMR (DMSO) d 10.99 (s, 1H), 8.89 (d,J=5.2 Hz, 1H), 8.63 (s, 1H), 8.57 (s, 1H), 8.34 (s, 1H), 8.29 (m, 1H),8.06 (d, J=8.8 Hz, 1H), 7.94 (dd, J=5.6 Hz, 1H), 7.70 (d, J=8.0 Hz, 1H),7.55 (t, 18.0 Hz, 1H), 4.29 (q, 8.8 Hz, 1H), 3.66 (m, 1H), 3.10 (m, 4H),2.55 (s, 3H), 1.08 (m, 2H), 0.98 (m, 2H). ¹⁹F NMR (DMSO) d −70.55 (d,J=8.8 Hz, 3F).

3-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide

C₂₂H₂₀N₈O. 413.1 (M+1). ¹H NMR (DMSO) d 10.96 (s, 1H), 8.67 (s, 1H),8.66 (s, 1H), 8.41 (s, 1H), 8.27 (d, J=8.0 Hz, 1H), 8.10 (m, 3H), 7.83(d, J=8.0 Hz, 1H), 7.76 (t, J=8.0 Hz, 1H), 4.27 (m, 1H), 2.03 (m, 1H),1.00 (m, 6H), 0.82 (m, 2H).

C. Similarly, following the procedure of Example 14, optionallyreplacing4-bromo-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamidewith other compounds of formula (5), and optionally replacing imidazolewith other amines, other compounds of Formula I are prepared.

EXAMPLE 15 Preparation of Compounds of Formula (I) via TriazoleFormation from an Acyl Hydrazide A. Preparation of a Compound of Formula(I) in which X², X³, X⁴, X⁶, X⁷ and X⁸ are C(R⁴), X¹ and X⁵ are N, R¹ is2-Methoxy-1-methylethyl, R² is Hydrogen, and R³ is2-Cyclopropylpyridin3-yl A. Preparation of(S)-6-cyclopropyl-N-(6-(4-(1-methoxypropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide

To a suspension of6-cyclopropyl-N-(6-(hydrazinecarbonyl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide,a compound of formula (3) (75 mg, 0.20 mmol) in toluene (0.20 M) wasadded N,N-dimethylformamide/N,N-dimethylacetamide (67 μL, 0.50 mmol),(S)-2-methoxy-1-methyl-ethylamine (72 mg μL, 0.80 mmol), and acetic acid(11 μL, 0.20 mmol). The reaction was heated to 150° C. for 30 minutes ina microwave reactor. The reaction mixture was concentrated under reducedpressure, and the residue suspended in acetonitrile/diethyl ether (15mL, 1:1 ratio), filtered and washed with acetonitrile/diethyl ether(2×10 mL). The solid thus obtained was dried under reduced pressure toafford 57 mg (63% yield) of(S)-6-cyclopropyl-N-(6-(4-(1-methoxypropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamideas a white solid.

C₂₅H₂₅N₇O₂. 456.2 (M+1). ¹H NMR (DMSO) d 10.71 (s, 1H), 8.95 (d, J=2 Hz,1H), 8.85 (s, 1H), 8.84 (d, J=5 Hz, 1H), 8.49 (s, 1H), 8.35 (d, J=8 Hz,1H), 8.21 (dd, J=2, 8 Hz, 1H), 8.08-8.12 (m, 2H), 7.92 (d, J=8 Hz, 1H),7.50 (d, J=8 Hz, 1H), 5.65-5.71 (m, 1H), 3.73 (dd, J=7, 10 Hz, 1H), 3.60(dd, J=5, 10 Hz, 1H), 3.24 (s, 3H), 2.18-2.25 (m, 1H), 1.51 (d, J=7 Hz,3H), 0.98-1.06 (m, 4H).

B. Preparation of other Compounds of Formula (I) Via Triazole formationfrom an Acyl Hydrazide

Similarly, optionally replacing6-cyclopropyl-N-(6-(hydrazinecarbonyl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamidewith other compounds of formula (3) and optionally replacing(S)-2-methoxy-1-methyl-ethylamine with other alkyl amines, and followingthe procedures of Example 15, the following compounds of Formula (I)were prepared.

(S)-4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(3-methylbutan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamide

C₂₅H₂₇N₇O×HCl. 442.1 (M-(1). ¹H NMR (DMSO) d 10.98 (s, 1H), 8.85 (s,1H), 8.79 (d, J=5.6 Hz, 1H), 8.55 (s, 1H), 8.36 (d, J=2.0 Hz, 1H), 8.16(s, 1H), 8.10 (d, J=8.8 Hz, 1H), 7.99 (dd, J=5.6 Hz, 1H), 7.86 (s, 1H),7.57 (t, J=8.0 Hz, 1H), 7.32 (d, J=8.0 Hz, 1H), 4.00 (m, 1H), 1.95 (m,1H), 1.87 (m, 1H), 1.51 (d, J=6.8 Hz, 3H), 0.82 (d, J=6.8 Hz, 6H), 0.74(m, 2H), 0.55 (m, 2H).

6-cyclopropyl-N-(3-(4-(2-phenylcyclopropyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₃₁H₂₆N₆O. 499.1 (M+1). ¹H NMR (DMSO) d 10.70 (s, 1H), 8.94 (d, J=2.4Hz, 1H), 8.81 (d, J=5.2 Hz, 1H), 8.78 (s, 1H), 8.41 (d, J=1.2 Hz, 1H),8.38 (s, 1H), 8.19 (m, 1H), 8.06 (m, 2H), 7.57 (d, J=8.0 Hz, 1H), 7.50(d, J=8.0 Hz, 1H), 7.41 (t, J=8.0 Hz, 1H), 7.21 (m, 2H), 7.08 (m, 3H),3.86 (m, 1H), 2.48 (m, 1H), 2.20 (m, 1H), 1.61 (m, 2H), 1.01 (m, 4H).

C. Preparation of other Compounds of Formula (I) via Triazole Formationfrom an Acyl Hydrazide

Similarly, optionally replacing6-cyclopropyl-N-(6-(hydrazinecarbonyl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamidewith other compounds of formula (3) and optionally replacing(S)-2-methoxy-1-methyl-ethylamine with other alkyl amines, and followingthe procedures of Example 15, other compounds of Formula (I) areprepared.

EXAMPLE 16 Preparation of Compounds of Formula (I) via TriazoleFormation from Oxadiazoles A. Preparation of a Compound of Formula (I)in which X², X³, X⁴, X⁶, X⁷ and X⁸ are C(R⁴), X¹ and X⁵ are N, R¹ is2-Hydroxy-1-methylethyl. R² is Hydrogen, and R³ is Pyridin3-yl A.Preparation of(R)—N-(3-(4-(1-hydroxypropan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

A suspension ofN-(3-(1,3,4-oxadiazol-2-yl)phenyl)-3,4′-bipyridine-2′-carboxamide (210mg, 0.61 mmol), (R)-2-amino-1-propanol (0.3 mL), and trifluoroaceticacid (0.05 mL) in n-butanol was heated in a microwave to 150° C. for 1hour. The solvent was removed under reduced pressure and the residue waspurified by reverse-phase HPLC to give(R)—N-(3-(4-(1-hydroxypropan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamideas a white powder (55 mg, 0.138 mmol, 23% yield).

C₂₂H₂₀N₆O₂. 401.5 (M+1). ¹H NMR (DMSO) d 10.97 (s, 1H), 9.11 (d, J=2.0Hz, 1H), 8.87 (d, J=4.4 Hz, 1H), 8.80 (s, 1H), 8.73 (dd, J=4.8, 1.6 Hz,1H), 8.48 (d, J=1.2 Hz, 1H), 8.34 (dt, J=4.0, 1.6 Hz, 1H), 8.21 (s, 1H),8.11 (m, 2H), 7.59 (m, 2H), 7.41 J=8.0 Hz, 1H), 5.14 (t, J=5.2 Hz, 1H),4.38 (m, 1H), 3.64 (m, 2H), 1.42 (d, J=6.8 Hz, 3H).

B. Similarly, optionally replacingN-(3-(1,3,4-oxadiazol-2-yl)phenyl)-3,4′-bipyridine-2′-carboxamide withother compounds of formula (4), and optionally replacing(R)-2-amino-1-propanol with other amines of formula R¹NH₂, and followingthe procedure of Example 16A, the following compound s of Formula (I)were prepared:

N-(3-(4-(3-amino-3-oxopropyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₂H₁₉N₇O₂. 414.2 (M+1). ¹H NMR (DMSO) d 10.99 (s, 1H), 9.11 (d, J=1.6Hz, 1H), 8.87 (m, 1H), 8.73 (dd, J=4.8, 1.6 Hz, 1H), 8.56 (s, 1H), 8.48(d, J=0.8 Hz, 1H), 8.34 (m, 1H), 8.28 (s, 1H), 8.12 (m, 2H), 7.60 (m,2H), 7.47 (d, J=7.2 Hz, 1H), 7.39 (s, 1H), 6.96 (s, 1H), 4.34 (t, J=6.8Hz, 2H), 2.56 (t, J=6.8 Hz, 2H).

N-(3-(4-(2-acetamidoethyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₃H₂₁N₇O₂. 428.1 (M+1). ¹H NMR (DMSO) d 10.97 (s, 1H), 9.11 (d, J=1.6Hz, 1H), 8.87 (d, J=4.8 Hz, 1H), 8.72 (dd, J=4.8, 1.2 Hz, 1H), 8.61 (s,1H), 8.48 (d, J=1.2 Hz, 1H), 8.34 (m, 1H), 8.26 (s, 1H), 8.12 (m, 2H),7.98 (m, 1H), 7.59 (m, 2H), 7.42 (d, J=8.0 Hz, 1H), 4.18 (t, J=6.0 Hz,2H), 3.34 (t, J=6.0 Hz, 2H), 1.67 (s, 3H).

(S)—N-(3-(4-(1-hydroxypropan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₂H₂₀N₆O₇O₂. 401.5 (M+1). ¹H NMR (DMSO) d 10.97 (s, 1H), 9.11 (d, J=2.0Hz, 1H), 8.87 (d, J=4.4 Hz, 1H), 8.80 (s, 1H), 8.73 (dd, J=4.8, 1.6 Hz,1H), 8.48 (d, J=1.2 Hz, 1H), 8.34 (dt, J=4.0, 1.6 Hz, 1H), 8.21 (s, 1H),8.11 (m, 2H), 7.59 (m, 2H), 7.41 (d, J=8.0 Hz, 1H), 5.14 (t, J=5.2 Hz,1H), 4.38 (m, 1H), 3.64 (m, 2H), 1.42 (d, J=6.8 Hz, 3H).

N-(3-(4-(tetrahydro-2H-pyran-4-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₄H₂₂N₆O₂, 427.1 (M+1). ¹H NMR (DMSO) d 11.02 (s, 1H), 9.11 (d, J=1.6Hz, 1H), 8.95 (s, 1H), 8.87 (d, J=4.8 Hz, 1H), 8.73 (dd, J=4.8, 1.6 Hz,1H), 8.47 (d, J=1.2 Hz, 1H), 8.35 (m, 1H), 8.26 (s, 1H), 8.11 (m, 2H),7.60 (m, 2H), 7.40 (d, J=7.6 Hz, 1H), 4.37 (m, 1H), 3.95 (m, 2H), 3.40(m, 2H), 2.00 (m, 4H).

(R)—N-(3-(4-(2-hydroxypropyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₂H₂₀N₆O₂. 401.2 (M+1). ¹H NMR (DMSO) d 10.97 (s, 1H), 9.11 (d, J=1.6Hz, 1H), 8.87 (d, J=4.8 Hz, 1H), 8.73 (dd, J=4.8, 1.2 Hz, 1H), 8.59 (s,1H), 8.48 (d, J=1.2 Hz, 1H), 8.34 (m, 1H), 8.27 (s, 1H), 8.11 (m, 2H),7.60 (m, 2H), 7.47 (d, J=8.0 Hz, 1H), 5.09 (br, 1H), 4.10 (dd, J=13.6,4.0 Hz, 1H), 3.96 (m, 1H), 3.86 (br, 1H), 1.01 (d, J=6.0 Hz, 3H).

(S)—N-(3-(4-(2-hydroxypropyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₂H₂₀N₆O₂. 401.2 (M+1). ¹H NMR (DMSO) d 10.97 (s, 1H), 9.11 (d, J=1.6Hz, 1H), 8.87 (d, J=4.8 Hz, 1H), 8.73 (dd, J=4.8, 1.2 Hz, 1H), 8.59 (s,1H), 8.48 (d, J=1.2 Hz, 1H), 8.34 (m, 1H), 8.27 (s, 1H), 8.11 (m, 2H),7.60 (m, 2H), 7.47 (d, J=8.0 Hz, 1H), 5.09 (br, 1H), 4.10 (dd, J=13.6,4.0 Hz, 1H), 3.96 (m, 1H), 3.86 (br, 1H), 1.01 (d, J=6.0 Hz, 3H).

N-(3-(4-cyclobutyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide;

C₂₃H₂₀N₆O. 397.2 (M+1). ¹H NMR (DMSO) d 10.99 (s, 1H), 9.11 (d, J=1.6Hz, 1H), 8.95 (s, 1H), 8.87 (d, J=5.2 Hz, 1H), 8.72 (m, 1H), 8.48 (s,1H), 8.33 (m, 1H), 8.25 (s, 1H), 8.10 (m, 2H), 7.58 (m, 2H), 7.38 (d,J=7.2 Hz, 1H), 4.78 (quintet, J=8.4 Hz, 1H), 2.45 (m, 4H), 1.80 (m, 2H).

N-(3-(4-cyclopentyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₄H₂₂N₆O. 411.2 (M+1). ¹H NMR (DMSO) d 10.99 (s, 1H), 9.11 (m, 1H),8.87 (d, J=4.8 Hz, 1H), 8.80 (s, 1H), 8.72 (d, J=4.4 Hz, 1H), 8.48 (s,1H), 8.34 (d, 8.0 Hz, 1H), 8.26 (s, 1H), 8.10 (m, 2H), 7.59 (m, 2H),7.39 (d, J=8.0 Hz, 1H), 4.61 (m, 1H), 2.18 (m, 2H), 1.84 (m, 4H), 1.63(m, 2H).

N-(3-(4-(2,2,2-trifluoroethyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₁H₁₅F₃N₆O. 425.8 (M+1). ¹H NMR (DMSO) d 10.99 (s, 1H), 9.11 (d, J=1.6Hz, 1H), 8.87 (d, J=5.2 Hz, 1H), 8.77 (s, 1H), 8.73 (dd, J=5.2, 1.6 Hz,1H), 8.48 (d, J=1.2 Hz, 1H), 8.34 (m, 1H), 8.19 (m, 2H), 8.12 (dd,J=5.2, 2.0 Hz, 1H), 7.61 (d, J=8.0 Hz, 1H), 7.59 (t, J=8.0 Hz, 1H), 7.44(d, J=8.0 Hz, 1H), 5.25 (q, J=9.0 Hz, 2H). ¹⁹F NMR (DMSO) d −70.31 (t,J=9.0 Hz, 3F).

N-(3-(4-((1-hydroxycyclopropyl)methyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₃H₂₀N₆O₂. 413.1 (M+1). ¹H NMR (DMSO) d 10.95 (s, 1H), 9.12 (d, J=2.0Hz, 1H), 8.87 (d, J=5.6 Hz, 1H), 8.74 (s, 1H), 8.73 (s, 1H), 8.48 (d,J=0.8 Hz, 1H), 8.36 (d, J=8.0 Hz, 1H), 8.25 (s, 1H), 8.11 (m, 2H), 7.62(dd, J=8.0, 5.2 Hz, 1H), 7.56 (t, J=8.0 Hz, 1H), 7.50 (d, J=8.0 Hz, 1H),4.19 (s, 2H), 0.64 (m, 2H), 0.59 (m, 2H).

(R)—N-(3-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₂H₁₇F₃N₆O. 439.2 (M+1). ¹H NMR (DMSO) d 10.97 (s, 1H), 9.11 (d, J=1.6Hz, 1H), 9.09 (s, 1H), 8.86 (dd, J=4.8, 1.2 Hz, 1H), 8.73 (dd, J=5.2,1.6 Hz, 1H), 8.48 (d, J=1.2 Hz, 1H), 8.34 (m, 1H), 8.19 (d, J=8.0 Hz,1H), 8.12 (m, 2H), 7.61 (d, J=8.0 Hz, 1H), 7.59 (t, J=8.0 Hz, 1H), 7.38(d, J=8.0 Hz, 1H), 5.29 (app sept, J=7.2 Hz, 1H), 1.82 (d, J=7.2 Hz,3H).

N-(3-(4-isopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₂H₂₀N₆O×HCl. 385.1 (M+1). ¹H NMR (DMSO) d 11.12 (s, 1H), 9.56 (s, 1H),9.28 (d, J=2.0 Hz, 1H), 8.92 (d, J=5.2 Hz, 1H), 8.86 (dd, J=5.2, 1.2 Hz,1H), 8.66 (d, J=8.0 Hz, 1H), 8.55 (s, 1H), 8.40 (s, 1H), 8.18 (m, 2H),7.86 (dd, J=8.0, 1.2 Hz, 1H), 7.66 (t, J=8.0 Hz, 1H), 7.47 (d, J=8.0 Hz,1H), 4.64 (sept, J=6.8 Hz, 1H), 1.51 (d, J=6.8 Hz, 6H).

N-(3-(4-(cyclopropylmethyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₃H₂₀N₆O×HCl. 397.1 (M+1). ¹H NMR (DMSO) d 11.11 (s, 1H), 9.48 (s, 1H),9.32 (s, 1H), 8.92 (d, J=5.2 Hz, 1H), 8.89 (d, J=5.2 Hz, 1H), 8.73 (d,J=8.0 Hz, 1H), 8.57 (s, 1H), 8.40 (s, 1H), 8.19 (m, 2H), 7.93 (dd,J=8.0, 5.6 Hz, 1H), 7.65 (t, J=8.0 Hz, 1H), 7.55 (d, J=8.0 Hz, 1H), 4.12(d, J=7.6 Hz, 2H), 1.26 (m, 1H), 0.58 (, 2H), 0.40 (m, 2H).

4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-isopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide

C₂₃H₂₃N₇O×HCl. 414.1 (M+1). ¹H NMR (DMSO) d 11.17 (s, 1H), 9.94 (s, 1H),9.66 (s, 1H), 8.99 (d, J=5.6 Hz, 1H), 8.59 (d, J=2.0 Hz, 1H), 8.37 (s,1H), 8.34 (s, 1H), 8.18 (m, 2H), 7.67 (t, J=8.0 Hz, 1H), 7.50 (d, J=8.0Hz, 1H), 4.64 (sept, J=6.8 Hz, 1H), 2.03 (m, 1H), 1.52 (d, J=6.8 Hz,6H), 1.06 (m, 2H), 0.91 (m, 2H).

4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(cyclopropylmethyl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamide

C₂₄H₂₃N₇O×HCl. 426.1 (M+1). ¹H NMR (DMSO) d 11.14 (s, 1H), 9.93 (s, 1H),9.46 (s, 1H), 9.00 (d, J=5.6 Hz, 1H), 8.59 (d, J=2.0 Hz, 1H), 8.37 (s,2H), 8.20 (m, 2H), 7.64 (t, J=8.0 Hz, 1H), 7.56 (d, J=8.0 Hz, 1H), 4.11(d, J=7.6 Hz, 2H), 2.04 (m, 1H), 1.24 (m, 1H), 1.06 (m, 2H), 0.91 (m,2H), 0.57 (m, 2H), 0.38 (m, 2H).

4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(cyclopropylmethyl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamide

C₂₈H₂₅N₇O×HCl. 476.1 (M+1). ¹H NMR (DMSO) d 11.02 (s, 1H), 9.75 (br,1H), 9.16 (s, 1H), 8.97 (d, J=5.2 Hz, 1H), 8.55 (d, J=2.0 Hz, 1H), 8.29(s, He, 8.18 (s, 1H), 8.13 (m, 2H), 7.51 (t, J=8.0 Hz, 1H), 7.27 (m,4H), 7.11 (d, J=6.8 Hz, 2H), 5.70 (q, J=6.8 Hz, 1H), 2.01 (m, 1H), 1.90(d, J=6.8 Hz, 3H), 1.05 (m, 2H), 0.95 (m, 2H).

6-cyclopropyl-N-(3-(4-isopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₅H₂₄N₆O. 425.1 (M+1). ¹H NMR (DMSO) d 10.98 (s, 1H), 8.93 (d, J=2.0Hz, 1H), 8.87 (s, 1H), 8.82 (d, J=5.2 Hz, 1H), 8.43 (d, J=1.2 Hz, 1H),8.17 (m, 3H), 8.05 (dd, J=5.2, 2.0 Hz, 1H), 7.57 (t, J=8.0 Hz, 1H), 7.49(d, J=8.0 Hz, 1H), 7.37 (d, J=8.0 Hz, 1H), 4.52 (sept, J=6.8 Hz, 1H),2.21 (m, 1H), 1.45 (d, J=6.8 Hz, 6H), 1.01 (m, 4H).

(S)-6-cyclopropyl-N-(3-(4-(1-phenylethyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₃₀H₂₆N₆O. 489.1 (M+1). ¹H NMR (DMSO) d 10.92 (s, 1H), 8.97 (s, 1H),8.93 (d, J=2.4 Hz, 1H), 8.82 (d, J=5.6 Hz, 1H), 8.43 (s, 1H), 8.19 (m,2H), 8.06 (m, 2H), 7.48 (m, 2H), 7.31 (m, 3H), 7.20 (d, J=8.0 Hz, 1H),7.10 (d, J=6.8 Hz, 2H), 5.66 (q, J=7.2 Hz, 1H), 2.21 (m, 1H), 1.88 (d,J=7.2 Hz, 3H), 1.02 (m, 4H).

N-(3-(4-cyclobutyl-4H-1,2,4-triazol-3-yl)phenyl)-6-cyclopropyl-3,4′-bipyridine-2′-carboxamide

C₂₆H₂₄N₆O. 437.1 (M+1). ¹H NMR (DMSO) d 10.96 (s, 1H), 8.93 (m, 2H),8.83 (d, J=4.8 Hz, 1H), 8.43 (d, J=1.2 Hz, 1H), 8.24 (s, 1H), 8.19 (dd,J=8.0, 2.8 Hz, 1H), 8.05 (m, 2H), 7.56 (t, J=8.0 Hz, 1H), 7.48 (d, J=8.0Hz, 1H), 7.38 (d, J=8.0 Hz, 1H), 4.77 (p, J=7.2 Hz, 1H), 2.44 (m, 4H),2.20 (m, 1H), 1.78 (m, 2H), 1.78 (m, 4H).

(S)-tert-butyl2-(3-(3-(6-cyclopropyl-3,4′-bipyridine-2′-carboxamido)phenyl)-4H-1,2,4-triazol-4-yl)propanoate

C₂₉H₃₀N₆O₃. 511.1 (M+1). ¹H NMR (DMSO) d 10.94 (s, 1H), 8.93 (d, J=2.0Hz, 1H), 8.85 (m, 2H), 8.42 (s, 1H), 8.17 (m, 2H), 8.06 (m, 2H), 7.56(t, J=8.0 Hz, 1H), 7.49 (d, J=8.0 Hz, 1H), 7.32 (d, J=8.0 Hz, 1H), 5.07(q, J=7.2 Hz, 1H), 2.21 (m, 1H), 1.75 (d, J=7.2 Hz, 3H), 1.30 (s, 9H),1.01 (m, 4H).

(S)-6-cyclopropyl-N-(3-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₅H₂₁F₃N₆O×HCl. 479.1 (M+1). ¹H NMR (DMSO) d 11.01 (s, 1H), 9.16 (s,1H), 9.13 (d, J=2.0 Hz, 1H), 8.89 (d, J=5.2 Hz, 1H), 8.65 (d, J=8.0 Hz,1H), 8.55 (s, 1H), 8.17 (m, 3H), 7.69 (d, J=8.0 Hz, 1H), 7.61 (t, J=8.0Hz, 1H), 7.39 (d, J=8.0 Hz, 1H), 5.30 (sept, J=7.2 Hz, 1H), 2.48 (m,1H), 1.82 (d, J=7.2 Hz, 3H), 1.10 (m, 4H). ¹⁹F NMR (DMSO) d −75.10 (d,J=7.2 Hz, 3F).

(R)-3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-(1-phenylethyl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide

C₂₈H₂₅N₇O×HCl. 476.2 (M+1). ¹H NMR (DMSO) d 11.16 (s, 1H), 9.79 (s, 1H),9.13 (s, 1H), 8.43 (s, 1H), 8.21 (s, 1H), 8.16 (dd, J=8, 14 Hz, 2H),8.05 (dd, J=2, 8 Hz, 1H), 7.98 (t, J=8 Hz, 1H), 7.86 (t, J=8 Hz, 1H),7.79 (d, J=7 Hz, 1H), 7.17-7.25 (m, 5H), 7.11 (q, J=7 Hz, 3H), 4.15 (brs, 1H), 2.02-2.07 (m, 1H), 1.89 (d, J=7 Hz, 3H), 1.05-1.09 (m, 2H),0.87-0.91 (m, 2H).

(S)-3-(4,5-dimethyl-1H-imidazol-1-yl)-N-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide

C₂₂H₂₀F₃N₇O. 456.2 (M+1). ¹H NMR (DMSO) d 10.99 (s, 1H), 9.13 (s, 1H),8.12 (d, J=7 Hz, 1H), 8.07 (t, J=8 Hz, 1H), 7.92-8.02 (m, 3H), 7.89 (brs, 1H), 7.75 (t, J=8 Hz, 1H), 7.68-7.72 (m, 1H), 7.16 (m, 1H), 2.14 (s,6H), 1.83 (d, J=7 Hz, 3H).

(S)-3-(4,5-dimethyl-1H-imidazol-1-yl)-N-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide

C₂₈H₂₅N₇O. 476.3 (M+1). ¹H NMR (DMSO) d 10.95 (s, 1H), 9.02 (s, 1H),8.24 (s, 1H), 8.18 (d, J=8 Hz, 1H), 8.15 (s, 1H), 7.96 (t, J=8 Hz, 1H),7.86-7.91 (m, 1H), 7.78 (d, J=7 Hz, 1H), 7.70 (t, J=8 Hz, 1H), 7.64 (brs, 1H), 7.16-7.27 (m, 5H), 7.07 (q, J=7 Hz, 1H), 1.88 (d, J=7 Hz, 3H),1.86-1.89 (m, 1H), 0.80-0.83 (m, 2H), 0.69-0.71 (m, 2H).

3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide

C₂₃H₂₃N₇O. 414.3 (M+1). ¹H NMR (DMSO) d 10.88 (s, 1H), 8.88 (s, 1H),8.34 (s, 1H), 8.18-8.21 (m, 1H), 8.16 (s, 1H), 8.05 (t, J=8 Hz, 1H),7.86-7.91 (m, 3H), 7.68 (t, J=8 Hz, 2H), 5.65 (sept, J=6 Hz, 1H),1.86-1.89 (m, 1H), 1.43 (d, J=6 Hz, 6H), 0.81-0.84 (m, 2H), 0.71-0.74(m, 2H).

(S)-6-cyclopropyl-N-(3-(4-(1-cyclopropylethyl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₇H₂₆N₆O. 451.1 (M+1). ¹H NMR (DMSO) d 10.95 (s, 1H), 8.93 (m, 2H),8.82 (d, J=4.8 Hz, 1H), 8.42 (d, J=1.2 Hz, 1H), 8.19 (dd, J=8.0, 2.4 Hz,1H), 8.14 (s, 1H), 8.10 (d, J=8.0 Hz, 1H), 8.05 (dd, J=5.2, 2.0 Hz, 1H),7.55 (t, J=8.0 Hz, 1H), 7.49 (d, J=8.0 Hz, 1H), 7.32 (d, J=8.0 Hz, 1H),3.70 (p, J=6.8 Hz, 1H), 2.21 (m, 1H), 1.51 (d, J=6.4 Hz, 3H), 1.35 (m,1H), 1.01 (m, 4H), 0.57 (m, 1H), 0.41 (m, 1H), 0.33 (m, 1H), 0.01 (m,1H).

6-cyclopropyl-N-(3-(4-(pentan-3-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₇H₂₈N₆O. 453.1 (M+1). ¹H NMR (DMSO) d 10.98 (s, 1H), 8.93 (d, J=2.0Hz, 1H), 8.82 (m, 2H), 8.42 (s, 1H), 8.22 (s, 1H), 8.19 (dd, J=8.0, 6.4Hz, 1H), 8.05 (m, 2H), 7.56 (t, 8.0 Hz, 1H), 7.49 (d, J=8.0 Hz, 1H),7.29 (d, J=8.0 Hz, 1h), 4.02 (p, J=7.6 Hz, 1H), 2.21 (m, 1H), 1.82 (p,J=7.6, 4H), 1.01 (m, 4H), 0.71 (t, J=7.6 Hz, 6H).

(S)-6-cyclopropyl-N-(3-(4-(1-methoxypropan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₆H₂₆N₆O₂. 455.1 (M+1). ¹H NMR (DMSO) d 10.95 (s, 1H), 8.93 (d, J=2.0Hz, 1H), 8.82 (m, 2H), 8.43 (s, 1H), 8.18 (m, 2H), 8.10 (d, J=8.0 Hz,1H), 8.05 (dd, J=5.2, 2.0 Hz, 1H), 7.56 (t, J=8.0 Hz, 1H), 7.48 (d,J=8.0 Hz, 1H), 7.37 (d, J=8.0 Hz, 1H), 4.55 (m, 1H), 3.63 (m, 1H), 3.54(m, 1H), 3.15 (s, 3H), 2.21 (m, 1H), 1.44 (d, J=6.8 Hz, 3H), 1.01 (m,4H).

(S)—N-(3-(4-sec-butyl-4H-1,2,4-triazol-3-yl)phenyl)-6-cyclopropyl-3,4′-bipyridine-2′-carboxamide

C₂₆H₂₆N₆O. 439.1 (M+1). ¹H NMR (DMSO) d 10.98 (s, 1H), 8.93 (d, J=2.0Hz, 1H), 8.85 (s, 1H), 8.82 (d, J=5.2 Hz, 1H), 8.43 (d, J=1.2 Hz, 1H),8.19 (m, 2H), 8.10 (d, J=8.0 Hz, 1H), 8.05 (dd, J=5.2 Hz, 1H), 7.57 (t,J=8.0 Hz, 1H), 7.49 (d, J=8.0 Hz, 1H), 7.34 (d, J=8.0 Hz, 1H), 4.24(sex, J=8.0 Hz, 1H), 2.21 (m, 1H), 1.79 (m, 2H), 1.48 (d, J=6.8 Hz, 3H),1.01 (m, 4H), 0.67 (t, J=7.2 Hz, 3H).

(S)-6-cyclopropyl-N-(3-(4-(3-methylbutan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₇H₂₈N₆O. 453.1 (M+1). ¹H NMR (DMSO) d 10.97 (s, 1H), 8.93 (d, J=2.4Hz, 1H), 8.84 (s, 1H), 8.82 (d, J=5.2 Hz, 1H), 8.43 (d, J=1.2 Hz, 1H),8.18 (m, 2H), 8.10 (d, J=8.0 Hz, 1H), 8.05 (dd, J=5.2, 2.0 Hz, 1H), 7.56(t, J=8.0 Hz, 1H), 7.49 (d, J=8.0 Hz, 1H), 7.32 (d, J=8.0 Hz, 1H), 4.01(m, 1H), 2.21 (m, 1H), 1.97 (m, 1H), 1.51 (d, J=6.8 Hz, 3H), 1.01 (m,4H), 0.83 (d, J=6.8 Hz, 3H), 0.57 (d, J=6.8 Hz, 3H).

(S)-6-cyclopropyl-N-(3-(4-(1-(2,6-dimethylphenoxy)propan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₃₃H₃₂N₆O₂. 545.1 (M+1). ¹H NMR (DMSO) d 10.95 (s, 1H), 9.01 (s, 1H),8.92 (s, J=2.4 Hz, 1H), 8.81 (d, J=5.2 Hz, 1H), 8.42 (d, J=1.2 Hz, 1H),8.26 (d, J=5.2 Hz, 1H), 8.18 (dd, J=8.0, 2.4 Hz, 1H), 8.14 (d, J=8.0 Hz,1H), 8.05 (dd, J=5.2, 2.0 Hz, 1H), 7.57 (t, J=8.0 Hz, 1H), 7.49 (d,J=8.0 Hz, 1H), 7.45 (d, J=8.0 Hz, 1H), 6.96 (d, J=7.2 Hz, 2H), 6.88 (t,J=7.2 Hz, 1H), 4.81 (m, 1H), 3.97 (m, 2H), 2.20 (m, 1H), 1.98 (s, 6H),1.62 (d, J=6.8 Hz, 3H), 1.01 (m, 4H).

(S)-6-cyclopropyl-N-(3-(4-(3,3-dimethylbutan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₈H₃₀N₆O. 467.1 (M+1). ¹H NMR (DMSO) d 10.96 (s, 1H), 8.93 (d, J=2.0Hz, 1H), 8.82 (m, 2H), 8.43 (d, J=1.2 Hz, 1H), 8.19 (dd, J=8.0, 2.4 Hz,1H), 8.14 (m, 2H), 8.05 (dd, J=5.2, 2.0 Hz, 1H), 7.56 (t, J=8.0 Hz, 1H),7.49 (d, J=8.0 Hz, 1H), 7.31 (d, J=8.0 Hz, 1H), 4.25 (q, J=6.8 Hz, 1H),2.20 (m, 1H), 1.56 (d, J=6.8 Hz, 3H), 1.01 (m, 4H), 0.80 (s, 9H).

(S)-4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamide

C₂₃H₂₀F₃N₇O. 468.1 (M+1). ¹H NMR (DMSO) d 10.94 (s, 1H), 9.09 (s, 1H),8.80 (d, J=5.6 Hz, 1H), 8.54 (d, J=1.2 Hz, 1H), 8.36 (d, J=2.0 Hz, 1H),8.17 (d, J=8.0 Hz, 1H), 8.10 (s, 1H), 7.99 (dd, J=5.6, 2.4 Hz, 1H), 7.85(s, 1H), 7.60 (t, J=8.0 Hz, 1H), 7.38 (d, J=7.2 Hz, 1H), 5.28 (m, 1H),1.86 (m, 1H), 1.82 (d, J=6.8 Hz, 3H), 0.84 (m, 2H), 0.74 (m, 2H). ¹⁹FNMR (DMSO) d −75.13 (d, J=7.2 Hz, 3F).

C. Similarly, optionally replacingN-(3-(1,3,4-oxadiazol-2-yl)phenyl)-3,4′-bipyridine-2′-carboxamide withother compounds of formula (4), and optionally replacing(R)-2-amino-1-propanol with other amines of formula R¹NH₂, and followingthe procedure of Example 16A, other compounds of Formula (I) areprepared:

6-cyclopropyl-N-(3-(4-phenyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

6-cyclopropyl-N-(3-(4-(pyridin-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

6-cyclopropyl-N-(3-(4-(pyridin-3-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

6-cyclopropyl-N-(3-(4-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

6-cyclopropyl-N-(3-(4-(pyrimidin-5-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

N-(3-(4-(but-2-ynyl)-4H-1,2,4-triazol-3-yl)phenyl)-6-cyclopropyl-3,4′-bipyridine-2′-carboxamide

6-cyclopropyl-N-(3-(4-(1-(pyridin-3-yloxy)propan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

6-cyclopropyl-N-(3-(4-(1-(2,2,2-trifluoroethoxy)propan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-phenyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide

4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(pyridin-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamide

4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(pyridin-3-yl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamide

4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(pyridin-4-yl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamide

4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(pyrimidin-5-yl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamide

N-(3-(4-(but-2-ynyl)-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-cyclopropyl-1H-imidazol-1-yl)picolinamide

4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(1-(pyridin-3-yloxy)propan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamideand

4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(1-(2,2,2-trifluoroethoxy)propan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamideEXAMPLE 17 Preparation of Compounds of Formula (I) A. Preparation of aCompound of Formula (I) in which X², X³, X⁴, X⁶, X⁷ and X⁸ are C(R⁴), X¹and X⁵ are N, R¹ is Cyclopropyl, R² is Hydrogen, and R³ is2-Cyclobutoxypyridin3-yl A. Preparation of6-cyclobutoxy-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

Sodium hydride (60% in mineral oil, 15 mg, 0.38 mmol) was added to 0.5mL of cyclobutanol and the reaction mixture was stirred for 10 minutesat room temperature.(N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-fluoro-3,4′-bipyridine-2′-carboxamide)(24 mg, 0.06 mmol) in cyclobutanol (0.2 mL) was added and the reactionmixture was heated to 90° C. for 30 minutes. The reaction mixture wasconcentrated under reduced pressure, neutralized with 1 M HCl andpurified by reverse-phase HPLC to give the product as a white powder (15mg, 55% yield).

C₂₆H₂₄N₆O₂. 453.1 (M+1). ¹H NMR (DMSO) d 10.92 (s, 1H), 8.79 (d, J=5.2Hz, 1H), 8.72 (d, J=2.4 Hz, 1H), 8.62 (s, 1H), 8.58 (s, 1H), 8.41 (d,J=1.2 Hz, 1H), 8.26 (dd, J=4.8, 2.4 Hz, 1H), 8.07 (d, J=8.0 Hz, 1H),8.03 (dd, J=5.2, 2.0 Hz, 1H), 7.68 (d, J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz,1H), 6.95 (d, J=8.8 Hz, 1H), 5.22 (p, J=7.6 Hz, 1H), 3.66 (m, 1H), 2.45(m, 2H), 2.10 (m, 2H), 1.85 (m, 1H), 1.70 (m, 1H), 1.08 (m, 2H), 0.95(m, 2H).

EXAMPLE 18 Preparation of Compounds of Formula (I) A. Preparation of aCompound of Formula (I) in which X², X³, X⁴, X⁶, X⁷ and X⁸ are C(R⁴),X^(I) and X⁵ are N, R¹ is Cyclopropyl, R² is Hydrogen, and R³ isN-cyclopropylpyridin-2-ylamine A. Preparation ofN-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(cyclopropylamino)-3,4′-bipyridine-2′-carboxamide

6-Chloro-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide(60.0 mg, 0.144 mmol) was dissolved in cyclopropylamine (250 μL), andthe mixture was heated to 110° C. for 2 days. The amine was removedunder reduced pressure, and the residue was purified by reverse phaseHPLC. The product(N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(cyclopropylamino)-3,4′-bipyridine-2′-carboxamide,31.2 mg, 50% yield) was isolated as a white solid.

C₂₅H₂₃N₇O. 438.1 (M+1). ¹H NMR (DMSO) d 10.88 (s, 1H), 8.70 (d, J=5 Hz,1H), 8.60-8.64 (m, 2H), 8.58 (s, 1H), 8.35 (d, J=1 Hz, 1H), 8.02-8.08(m, 2H), 7.95 (dd, J=2.5 Hz, 1H), 7.68 (d, J=8 Hz, 1H), 7.54 (t, J=8 Hz,1H), 7.30 (d, J=2 Hz, 1H), 6.73 (d, J=9 Hz, 1H), 3.64-3.68 (m, 1H),2.58-2.62 (m, 1H), 1.09 (q, J=6 Hz, 2H), 0.91-0.96 (m, 2H), 0.72-0.77(m, 2H) 0.46-0.49 (m, 2H).

B. Similarly, following the procedure of Example 18A, optionallyreplacing6-chloro-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamidewith other compounds of formula (5), and optionally replacingcyclopropylamine with other amines of formula R¹NH₂, the followingcompounds of Formula (I) were prepared:

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(pyrrolidin-1-yl)-3,4′-bipyridine-2′-carboxamide

C₂₆H₂₅N₇O. 452.2 (M+1). ¹H NMR (DMSO) d 10.88 (s, 1H), 8.68-8.71 (m,2H), 8.63 (s, 1H), 8.58 (s, 1H), 8.35 (s, 1H), 8.06 (d, J=8 Hz, 2H),7.94-7.96 (m, 1H), 7.66-7.69 (m, 1H), 7.54 (t, J=8 Hz, 1H), 6.60 (d,J=7.2 Hz, 1H), 3.64-3.70 (m, 1H), 3.42-3.54 (m, 4H), 1.92-2.04 (m, 4H),1.06-1.12 (m, 2H), 0.91-0.97 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(ethylamino)-3,4′-bipyridine-2′-carboxamide

C₂₄H₂₃N₇O. 426.1 (M+1). ¹H NMR (DMSO) d 10.88 (s, 1H), 8.69 (d, J=5 Hz,1H), 8.62 (s, 1H), 8.59 (d, J=2 Hz, 1H), 8.58 (s, 1H), 8.33 (d, J=1 Hz,1H), 8.06 (d, J=8 Hz, 1H), 7.91-7.96 (m, 2H), 7.68 (d, J=8 Hz, 1H), 7.54(t, J=8 Hz, 1H), 7.04 (t, J=6 Hz, 1H), 6.60 (d, J=9 Hz, 1H), 3.66 (dddd,J=4, 8, 12, 16 Hz, 1H), 3.35 (q, J=7 Hz, 2H), 1.16 (t, J=7 Hz, 3H), 1.08(app q, J=8 Hz, 2H), 0.93-0.97 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(cyclopropylamino)-3,4′-bipyridine-2′-carboxamide

C₂₅H₂₃N₇O. 438.1 (M+1). ¹H NMR (DMSO) d 10.88 (s, 1H), 8.70 (d, J=5 Hz,1H), 8.60-8.64 (m, 2H), 8.58 (s, 1H), 8.35 (d, J=1 Hz, 1H), 8.02-8.08(m, 2H), 7.95 (dd, J=2, 5 Hz, 1H), 7.68 (d, J=8 Hz, 1H), 7.54 (t, J=8Hz, 1H), 7.30 (d, J=2 Hz, 1H), 6.73 (d, J=9 Hz, 1H), 3.64-3.68 (m, 1H),2.58-2.62 (m, 1H), 1.09 (q, J=6 Hz, 2H), 0.91-0.96 (m, 2H), 0.72-0.77(m, 2H) 0.46-0.49 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(methylthio)-3,4′-bipyridine-2′-carboxamide

C₂₃H₂₀N₆OS. 429.3 (M+1). ¹H NMR (DMSO) d 10.93 (s, 1H), 8.99 (s, 1H),8.82 (d, J=5 Hz, 1H), 8.63 (s, 1H), 8.59 (s, 1H), 8.46 (s, 1H),8.19-8.22 (m, 1H), 8.05-8.09 (m, 2H), 7.69 (d, J=8 Hz, 1H), 7.55 (t, J=8Hz, 1H), 7.49 (d, J=8 Hz, 1H), 3.65-3.68 (m, 1H), 2.56 (s, 3H),1.08-1.12 (m, 2H) 0.93-0.96 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(isobutylthio)-3,4′-bipyridine-2′-carboxamide

C₂₆H₂₆N₆OS. 472.1 (M+1). ¹H NMR (DMSO) d 10.94 (s, 1H), 8.98 (s, 1H),8.82 (d, J=5 Hz, 1H), 8.63 (s, 1H), 8.59 (s, 1H), 8.45 (s, 1H), 8.17(dd, J=2, 8 Hz, 1H), 8.05-8.10 (m, 2H), 7.69 (d, J=8 Hz, 1H), 7.55 (t,J=8 Hz, 1H), 7.48 (d, J=9 Hz, 1H), 3.65-3.70 (m, 1H), 3.14 (d, J=6 Hz,2H), 1.94 (sept, J=6 Hz, 1H), 1.07-1.10 (m, 2H), 1.02 (d, J=6 Hz, 6H),0.92-0.97 (m, 2H).

C. Similarly, following the procedure of Example 18A, optionallyreplacing6-chloro-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamidewith other compounds of formula (5), and optionally replacingcyclopropylamine with other amines of formula R¹NH₂, other compound s ofFormula (I) are prepared.

EXAMPLE 19 Preparation of Compounds of Formula (I) Utilizing IronCatalyzed Alkyl-Grignard Cross-Coupling Preparation of a Compound ofFormula (I) in which X², X³, X⁴, X⁶, X⁷ and X⁸ are C(R⁴), X¹ and X⁵ areN, R¹ is Cyclopropyl R² is Hydrogen, and R³ is N-cyclopropylpyrimidineA. Preparation ofN-(3-(4-cyclopropyl-4H-1,2,4-thiazol-3-yl)phenyl)-4-(2-cyclopropylpyrimidin-5-yl)picolinamide

Cyclopropyl magnesium bromide (0.5 M solution in tetrahydrofuran, 6.3mL, 3 equiv) was added to a solution of4-(2-chloropyrimidin-5-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide(440 mg, 1.06 mmol) and Fe(acac)₃ (37 mg, 10 mmol %) in N-methylpyridine(20 mL) and tetrahydrofuran (5 mL). After stirring for 5 minutes, thebrown solution was quenched with 1 M hydrochloric acid (6 mL) andconcentrated under reduced pressure at 70° C. The residue was purifiedby reverse-phase HPLC to giveN-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(2-cyclopropylpyrimidin-5-yl)picolinamideas a pale-yellow powder (200 mg, 45% yield).

C₂₄H₂₁N₇O. 424.1 (M+1). ¹H NMR (DMSO) d 10.95 (s, 1H), 9.18 (s, 2H),8.86 (d, J=5.2 Hz, 1H), 8.63 (s, 1H), 8.58 (s, 1H), 8.51 (d, J=1.2 Hz,1H), 8.11 (dd, J=5.2, 2.0 Hz, 1H), 8.07 (d, J=8.0 Hz, 1H), 7.69 (d,J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 3.66 (m, 1H), 2.32 (m, 1H), 1.10(m, 6H), 0.95 (m, 2H).

B. Similarly, following the procedure of Example 19A, optionallyreplacing4-(2-chloropyrimidin-5-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamidewith other compounds of formula (5), and optionally replacingcyclopropyl magnesium bromide with other Grignard reagents, thefollowing compound s of Formula (I) were prepared:

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-isopropyl-3,4′-bipyridine-2′-carboxamide

C₂₅H₂₄N₆O. 425.1 (M+1). ¹H NMR (DMSO) d 10.94 (s, 1H), 9.02 (d, J=2.0Hz, 1H), 8.84 (d, J=5.2 Hz, 1H), 8.63 (s, 1H), 8.58 (s, 1H), 8.46 (d,J=1.2 Hz, 1H), 8.25 (dd, J=8.0, 2.4 Hz, 1H), 8.08 (m, 2H), 7.69 (d,J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 7.48 (d, J=8.0 Hz, 1H), 3.67 (m,1H), 3.12 (sept, J=7.2 Hz, 1H), 1.29 (d, J=7.2 Hz, 6H), 1.08 (m, 2H),0.95 (m, 2H).

6-cyclobutyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₆H₂₄N₆O. 437.1 (M+1). ¹H NMR (DMSO) d 10.94 (s, 1H), 9.05 (d, J=2.0Hz, 1H), 8.84 (d, J=51 Hz, 1H), 8.63 (s, 1H), 8.59 (s, 1H), 8.46 (d,J=1.2 Hz, 1H), 8.24 (dd, J=8.0, 2.0 Hz, 1H), 8.08 (m, 2H), 7.69 (d,J=8.0 Hz, 1H), 7.55 (1, J=8.0 Hz, 1H), 7.44 (d, J=8.0 Hz, 1H), 3.72 (p,J=8.8 Hz, 1H), 3.66 (m, 1H), 2.33 (m, 4H), 2.04 (m, 1H), 1.89 (m, 1H),1.08 (m, 2H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-ethyl-3,4′-bipyridine-2′-carboxamide

C₂₄H₂₂N₆O. 411.1 (M+1). ¹H NMR (DMSO) d 10.94 (s, 1H), 9.01 (d, J=2.0Hz, 1H), 8.84 (d, J=5.2 Hz, 1H), 8.63 (s, 1H), 8.59 (s, 1H), 8.46 (d,J=1.2 Hz, 1H), 8.25 (dd, J=8.4, 2.4 Hz, 1H), 8.08 (m, 2H), 7.69 (d, 8.0Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 7.47 (d, J=8.0 Hz, 1H), 3.66 (m, 1H),2.85 (q, 7.2 Hz, 2H), 1.28 (t, J=7.2 Hz, 3H), 1.08 (m, 2H), 0.95 (m,2H).

6-cyclopentyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₇H₂₆N₆O. 451.1 (M+1). ¹H NMR (DMSO) d 10.94 (s, 1H), 9.02 (d, J=2.0Hz, 1H), 8.84 (d, J=5.2 Hz, 1H), 8.63 (s, 1H), 8.58 (s, 1H), 8.45 (d,J=1.2 Hz, 1H), 8.23 (dd, J=8.0, 2.4 Hz, 1H), 8.07 (m, 2H), 7.69 (d,J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 7.47 (d, J=8.0 Hz, 1H), 3.66 (m,1H), 3.25 (m, 1H), 2.05 (m, 2H), 1.78 (m, 4H), 1.70 (m, 2H), 1.08 (m,2H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(1-methyl-2-oxopyrrolidin-3-yl)-3,4′-bipyridine-2′-carboxamide

C₂₇H₂₅N₇O₂. 480.1 (M+1). ¹H NMR (DMSO) d 10.95 (s, 1H), 9.04 (d, J=2.4Hz, 1H), 8.86 (d, J=4.8 Hz, 1H), 8.63 (s, 1H), 8.59 (s, 1H), 8.47 (d,J=1.2 Hz, 1H), 8.29 (dd, J=8.0, 2.4 Hz, 1H), 8.08 (m, 2H), 7.69 (d,J=8.0 Hz, 1H), 7.55 (m, 2H), 3.92 (t, J=8.8 Hz, 1H), 3.67 (m, 1H), 3.50(m, 2H), 2.80 (s, 3H), 2.42 (q, 8.8 Hz, 2H), 1.08 (m, 2H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-propyl-3,4′-bipyridine-2′-carboxamide

C₂₅H₂₄N₆O. 425.1 (M+1). ¹H NMR (DMSO) d 10.94 (s, 1H), 9.01 (d, J=2.0Hz, 1H), 8.84 (d, J=5.2 Hz, 1H), 8.63 (s, 1H), 8.59 (s, 1H), 8.46 (d,J=0.8 Hz, 1H), 8.24 (dd, J=8.0, 2.4 Hz, 1H), 8.08 (m, 2H), 7.69 (d,J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 7.45 (d, J=8.0 Hz, 1H), 3.66 (m,1H), 2.80 (t, J=8.0 Hz, 2H), 1.75 (q, J=8.0 Hz, 2H), 1.08 (m, 2H), 0.96(m, 5H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-neopentyl-3,4′-bipyridine-2′-carboxamide

C₂₇H₂₈N₆O. 453.1 (M+1). ¹H NMR (DMSO) d 10.95 (s, 1H), 9.03 (d, J=2.0Hz, 1H), 8.84 (d, J=4.8 Hz, 1H), 8.63 (s, 1H), 8.59 (s, 1H), 8.47 (s,1H), 8.25 (dd, J=8.0, 2.8 Hz, 1H), 8.10 (m, 2H), 7.69 (d, J=8.0 Hz, 1H),7.55 (t, J=8.0 Hz, 1H), 7.41 (d, J=8.0 Hz, 1H), 3.66 (m, 1H), 2.73 (s,2H), 1.08 (m, 2H), 1.00 (m, 11H).

6-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5-fluoro-3,4′-bipyridine-2′-carboxamide

C₂₅H₂₁FN₆O. 441.1 (M+1). ¹H NMR (DMSO) d 10.94 (s, 1H), 8.84 (m, 2H),8.63 (s, 1H), 8.58 (s, 1H), 8.48 (d, J=1.2 Hz, 1H), 8.25 (dd, J=11.2,2.0 Hz, 1H), 8.09 (m, 2H), 7.69 (d, J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz,1H), 3.66 (m, 1H), 2.32 (m, 1H), 1.08 (m, 6H), 0.95 (m, 2H).

5-chloro-6-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₅H₂₁ClN₆O. 457.0 (M+1). ¹H NMR (DMSO) d 10.94 (s, 1H), 8.92 (d, J=2.0Hz, 1H), 8.84 (d, J=5.2 Hz, 1H), 8.63 (s, 1H), 8.59 (s, 1H), 8.45 (s,1H), 8.44 (d, J=2.0 Hz, 1H), 8.09 (m, 2H), 7.69 (d, J=8.0 Hz, 1H), 7.55(t, J=8.0 Hz, 1H), 3.66 (m, 1H), 2.55 (m, 1H), 1.08 (m, 6H), 0.95 (m,2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-ethyl-5-fluoro-3,4′-bipyridine-2′-carboxamide

C₂₄H₂₁FN₆O. 429.1 (M+1). ¹H NMR (DMSO) d 10.95 (s, 1H), 8.92 (s, 1H),8.87 (d, J=4.8 Hz, 1H), 8.63 (s, 1H), 8.59 (s, 1H), 8.51 (s, 1H), 8.28(d, 10.8 Hz, 1H), 8.12 (d, J=5.2 Hz, 1H), 8.07 (d, J=8.0 Hz, 1H), 7.70(d, J=8.0 Hz, 1H), 7.56 (t, J=8.0 Hz, 1H), 3.66 (m, 1H), 2.89 (q, J=7.2Hz, 2H), 1.28 (t, J=7.2 Hz, 3H), 1.08 (m, 2H), 0.95 (m, 2H). ¹⁹F NMR(DMSO) d −126.5 (d, J=10.8 Hz, 1F).

5-chloro-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-ethyl-3,4′-bipyridine-2′-carboxamide

C₂₄H₂₁ClN₆O. 445.1 (M+1). ¹H NMR (DMSO) d 10.96 (s, 1H), 9.01 (s, 1H),8.86 (m, 1H), 8.63 (s, 1H), 8.59 (s, 1H), 8.51 (s, 1H), 8.47 (s, 1H),8.09 (m, 2H), 7.69 (d, J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 3.66 (m,1H), 2.97 (q, J=7.6 Hz, 2H), 1.31 (t, J=7.6 Hz, 3H), 1.08 (m, 2H), 0.95(m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5,6-diethyl-3,4′-bipyridine-2′-carboxamide

C₂₆H₂₆N₆O. 439.1 (M+1). ¹H NMR (DMSO) d 10.94 (s, 1H), 8.86 (s, 1H),8.84 (d, J=5.2 Hz, 1H), 8.63 (s, 1H), 8.59 (s, 1H), 8.47 (s, 1H), 8.07(m, 3H), 7.69 (d, J=8.0 Hz, 1H), 7.56 (t, J=8.0 Hz, 1H), 3.67 (m, 1H),2.85 (q, J=7.6 Hz, 2H), 2.75 (q, J=7.6 Hz, 2H), 1.26 (m, 6H), 1.09 (m,2H), 0.94 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(2-ethylpyrimidin-5-yl)picolinamide

C₂₃H₂₁N₇O. 412.1 (M+1). ¹H NMR (DMSO) d 10.96 (s, 1H), 9.27 (s, 2H),8.89 (d, J=5.2 Hz, 1H), 8.63 (s, 1H), 8.59 (s, 1H), 8.54 (d, J=0.8 Hz,1H), 8.14 (dd, J=5.2, 2.0 Hz, 1H), 8.08 (d, J=9.2 Hz, 1H), 7.70 (d,J=8.0 Hz, 1H), 7.55 (1, J=8.0 Hz, 1H), 3.66 (m, 1H), 3.00 (q, J=7.2 Hz,2H), 1.39 (t, J=7.2 Hz, 3H), 1.08 (m, 2H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5-ethyl-3,4′-bipyridine-2′-carboxamide

C₂₄H₂₂N₆O. 411.1 (M+1). ¹H NMR (DMSO) d 10.96 (s, 1H), 8.93 (d, J=2.4Hz, 1H), 8.86 (d, J=5.6 Hz, 1H), 8.63 (s, 1H), 8.60 (s, 1H), 8.59 (s,1H), 8.49 (d, J=1.2 Hz, 1H), 8.19 (s, 1H), 8.10 (m, 2H), 7.69 (d, J=8.0Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 3.67 (m, 1H), 2.75 (q, J=7.6 Hz, 2H),1.28 (t, J=7.6 Hz, 3H), 1.08 (m, 2H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(cyclopropylmethyl)-3,4′-bipyridine-2′-carboxamide

C₂₆H₂₄N₆O. 437.1 (M+1). ¹H NMR (DMSO) d 10.97 (s, 1H), 9.01 (d, J=2.4Hz, 1H), 8.85 (d, 5.6 Hz, 1H), 8.64 (s, 1H), 8.59 (s, 1H), 8.46 (s, 1H),8.28 (dd, J=8.0 Hz, 1H), 8.09 (m, 2H), 7.69 (d, J=8.0 Hz, 1H), 7.55 (m,2H), 3.67 (m, 1H), 2.73 (d, J=6.8 Hz, 2H), 1.09 (m, 3H), 0.94 (m, 2H),0.50 (m, 2H), 0.26 (m, 2H).

C. Similarly, following the procedure of Example 19A, optionallyreplacing4-(2-chloropyrimidin-5-yl)-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamidewith other compounds of formula (5), and optionally replacingcyclopropyl magnesium bromide with other Grignard reagents, othercompounds of Formula (I) are prepared.

EXAMPLE 20 Preparation of Compounds of Formula (I) Preparation of aCompound of Formula (I) in which X², X³, X⁴, X⁶, X⁷ and X⁸ are C(R⁴), X¹and X⁵ are N, R¹ is Cyclopropyl, R² is Hydrogen, and R³ is Morpholin-ylA. Preparation ofN-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-4-morpholinopicolinamide

4-Chloro-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide (0.112mmol, 35.0 mg) was treated with an excess (400 μL) of morpholine andheated to 100° C. for 2 hours. The reaction mixture was diluted withwater (400 μL) and purified by RP-HPLC to afford 37.0 (91% yield) ofN-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-4-morpholinopicolinamide.

C₁₉H₂₀N₆O₂. 365.2 (M+1). ¹H NMR (DMSO) d 10.81 (s, 1H), 8.58 (s, 1H),8.34 (d, J=5.6 Hz, 1H), 8.29-8.31 (m, 1H), 8.05-8.09 (m, 1H), 7.59 (d,J=2.4 Hz, 1H), 7.53 (t, J=8 Hz, 1H), 7.48-7.51 (m, 1H), 7.09 (dd, J=2.4,6 Hz, 1H), 3.79 (s, 3H), 3.74 (t, J=8.8 Hz, 4H), 3.40 (t, J=8.8 Hz, 4H).

B. Similarly, following the procedure of Example 20A, but optionallyreplacing4-chloro-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide withother compounds of formula (5), and optionally replacing morpholine withother amines, the following compounds of Formula (I) were prepared:

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-(methylsulfonyl)piperazin-1-yl)picolinamide

C₂₂H₂₅N₇O₃S. 468.1 (M+1). ¹H NMR (DMSO) d 10.77 (s, 1H), 8.62 (s, 1H),8.56 (s, 1H), 8.35 (d, J=6 Hz, 1H), 8.01 (d, J=8 Hz, 1H), 7.66 (d, J=8Hz, 1H), 7.62 (d, J=2 Hz, 1H), 7.52 (t, J=8 Hz, 1H), 7.13 (dd, J=3, 6Hz, 1H), 3.63-3.67 (m, 1H), 3.59 (t, J=4 Hz, 4H), 3.25 (t, J=5 Hz, 4H),2.93 (s, 3H), 1.06 (dd, J=6, 9 Hz, 2H), 0.91-0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(3-hydroxypiperidin-1-yl)picolinamide

C₂₂H₂₄N₆O₂. 405.1 (M+1). ¹H NMR (DMSO) d 10.74 (s, 1H), 8.62 (s, 1H),8.55 (s, 1H), 8.26 (d, J=6 Hz, 1H), 8.01 (d, J=8 Hz, 1H), 7.65 (d, J=8Hz, 1H), 7.54 (s, 1H), 7.52 (t, J=8 Hz, 1H), 7.02 (dd, J=3, 6 Hz, 1H),4.95 (d, J=4 Hz, 1H), 3.32-3.81 (m, 4H), 3.02-3.11 (m, 1H), 2.96 (dd,J=8, 12 Hz, 1H), 1.83-1.92 (m, 1H), 1.70-1.80 (m, 1H), 1.42-1.48 (m,2H), 1.07 (dd, J=7, 13 Hz, 2H), 0.90-0.95 (m, 2H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(3-hydroxypiperidin-1-yl)picolinamide

C₂₁H₂₃N₇O₂×HCO₂H. 406.1 (M+1). ¹H NMR (DMSO) d 10.64 (s, 1H), 8.68 (s,1H), 8.36 (d, J=8 Hz, 1H), 8.25 (d, J=6 Hz, 1H), 8.14 (s, 1H), 8.08 (t,J=8 Hz, 1H), 7.85 (d, J=7 Hz, 1H), 7.58 (d, J=2 Hz, 1H), 7.04 (dd, J=3,6 Hz, 1H), 4.95 (s, 1H), 3.98-4.04 (m, 1H), 3.79 (dd, J=3, 13 Hz, 1H),3.72 (d, J=14 Hz, 1H), 3.56-3.59 (m, 1H), 3.07-3.14 (m, 1H), 3.00 (dd,J=8, 13 Hz, 1H), 1.86-1.90 (m, 1H), 1.74-1.78 (m, 1H), 1.42-1.48 (m,2H), 0.95-1.07 (m, 4H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4-ethyl-3-oxopiperazin-1-yl)picolinamide

C₂₃H₂₅N₇O₂×HCO₂H. 432.1 (M+1), ¹H NMR (DMSO) d 10.79 (s, 1H), 8.62 (s,1H), 8.56 (s, 1H), 8.34 (d, J=6 Hz, 1H), 8.13 (s, 1H), 8.01 (d, J=9 Hz,1H), 7.66 (d, J=8 Hz, 1H), 7.50-7.55 (m, 2H), 7.05 (dd, J=2, 6 Hz, 1H),4.02 (s, 2H), 3.72 (t, J=5 Hz, 2H), 3.63-3.67 (m, 1H), 3.50 (t, J=6 Hz,2H), 3.41 (q, J=8 Hz, 2H), 1.03-1.10 (m, 5H), 0.90-0.95 (m, 2H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-(4-ethyl-3-oxopiperazin-1-yl)picolinamide

C₂₂H₂₄N₈O₂. 433.1 (M+1). ¹H NMR (DMSO) d 10.78 (s, 1H), 8.69 (s, 1H),8.34 (t, J=7 Hz, 2H), 8.09 (t, J=8 Hz, 1H), 7.86 (d, J=7 Hz, 1H), 7.64(br s, 1H), 7.10 (br s, 1H), 4.01-4.12 (m, 3H), 3.76 (s, 2H), 3.51 (t,J=5 Hz, 2H), 3.41 (q, J=7 Hz, 2H), 1.08 (t, J=7 Hz, 3H), 0.95-1.06 (m,4H).

C. Similarly, following the procedure of Example 20A, but optionallyreplacing4-chloro-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide withother compounds of formula (5), and optionally replacing morpholine withother amines, other compounds of Formula (I) are prepared.

EXAMPLE 21 Preparation of Compounds of Formula (I) in which X¹ is C(R⁴)Preparation of a Compound of Formula (I) in which X, X³, X⁴, X⁶, X⁷ andX⁸ are C(R⁴), X² and X⁵ are N, R¹ is Cyclopropyl, R² is Hydrogen, and R³is Quinolin-3-yl A. Preparation ofN-6-(1-cyclopropyl-1H-imidazol-5-yl)pyridin-2-yl)-4-(quinolin-3-yl)picolinamide

Steps 1 and 2: To a stirred solution of5-bromo-1-cyclopropyl-1H-imidazole (780 mg, 1.90 mmol), intetrahydrofuran (3 mL) at −78° C. was added n-butyllithium (911 μL 2.5 Msolution, 2.28 mmol) and the reaction mixture was stirred for 30 minutesat −78° C. A solution of zinc bromide (ZnBr₂, (641 mg, 2.85 mmol, driedunder vacuum at 100° C. for 3 hours) in tetrahydrofuran (3 mL) wasadded, the mixture warmed to room temperature and stirred an additional2.5 hours. A solution of 6-(di-Boc-amino)-2-bromopyridine and Pd(PPh₃)₄in 3 mL tetrahydrofuran was added to the reaction via cannula and themixture was stirred overnight. The reaction was concentrated underreduced pressure and the residue was purified by flash chromatography(5% methanol in methylene chloride, gradient flash: 4%→10% methanol inmethylene chloride,). The product was isolated as mixture of the mono-and bis-Boc protected 6-(1-cyclopropyl-1H-imidazol-5-yl)pyridin-2-amine.This mixture was used directly in the next step

Step 3: The material from the above sequence was dissolved indichloroethane (2 mL), trifluoroacetic acid was added, and the mixturewas heated to 50° C. and stirred for 1 hour. The material was purifiedby reverse phase HPLC to afford 150 mg (40% yield) of6-(3-cyclopropyl-3H-imidazol-4-yl)-pyridin-2-ylamine as a white solid.M+1=201.2

Step 4: A solution of 4-chloro-pyridine-2-carboxylic acid (141 mg, 0.895mmol), 6-(3-cyclopropyl-3H-imidazol-4-yl)-pyridin-2-ylamine (150 mg,0.750 mmol), (2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate (HATU) (342 g, 0.899 mmol), and N-methylmorpholine(250 μL, 2.70 mmol) in N,N-dimethylformamide was stirred at roomtemperature for 12 hours. The solvent was removed under reducedpressure, the residue suspended in acetonitrile, and the solid isolatedby filtration, washed with water (80 mL), acetonitrile (80 mL) anddiethyl ether (80 mL), and dried under reduced pressure to afford4-chloro-N-(6-(1-cyclopropyl-1H-imidazol-5-yl)pyridin-2-yl)picolinamideas a white powder (120 mg, 47% yield). M+1=340.1

Step 5: A suspension of4-chloro-N-(6-(1-cyclopropyl-1H-imidazol-5-yl)pyridin-2-yl)picolinamide(38.9 mg, 0.115 mmol), boronic acid (29 mg, 0.138 mmol), dppf(Pd)Cl₂(4.2 mg, 0.00575), potassium carbonate (47.7 mg, 0.345 mmol) in degassedtoluene (1 mL), degassed water (0.5 mL) and degassed isopropanol (0.5mL) was heated at 95° C. for 2 hours. The aqueous phase was discardedand the solvent removed from the organic portion under reduced pressure.Purification by reverse phase HPLC providedN-(6-(1-cyclopropyl-1H-imidazol-5-yl)pyridin-2-yl)-4-(quinolin-3-yl)picolinamide(10.1 mg, 20%) as a white solid. C₂₆H₂₀N₆O×HCO₂H. 433.1 (M+1). ¹H NMR(DMSO) d 10.64 (s, 1H), 9.45 (d, J=2 Hz, 1H), 9.05 (d, J=2 Hz, 1H), 8.93(d, J=5 Hz, 1H), 8.72 (d, J=1 Hz, 1H), 8.30-8.33 (m, 2H), 8.18 (d, J=8Hz, 1H), 8.12 (d, J=8 Hz, 1H), 8.04 (t, J=8 Hz, 1H), 7.82-7.89 (m, 2H),7.73 (t, J=8 Hz, 1H), 7.37 (s, 1H), 7.04 (s, 1H), 4.23-4.27 (m, 1H),1.04-1.09 (m, 2H) 0.91-0.95 (m, 2H).

B. Similarly, following the procedure of Example 21A, the followingcompound of Formula (I) was prepared:

6-cyclopropyl-N-(6-(1-cyclopropyl-1H-imidazol-5-yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide

C₂₅H₂₂N₆O. 423.1 (M+1). ¹H NMR (DMSO) d 10.61 (s, 1H), 8.95 (d, J=2 Hz,1H), 8.83 (d, J=5 Hz, 1H), 8.49 (s, 1H), 8.32 (d, J=8 Hz, 1H), 8.21 (dd,J=2, 8 Hz, 1H), 8.10 (dd, J=2.5 Hz, 1H), 8.05 (t, J=8.0 Hz, 1H), 7.85(d, J=8 Hz, 1H), 7.50 (d, J=8 Hz, 1H), 4.20-4.25 (m, 1H), 2.19-2.23 (m,1H), 0.95-1.10 (m, 8H).

C. Similarly, following the procedure of Example 21A, other compounds ofFormula (I) are prepared.

EXAMPLE 22 Preparation of Compounds of Formula (I) in which X¹ is C(R⁴)Preparation of a Compound of Formula (I) in which X¹, X², X³, X⁴, X⁶, X⁷and X⁸ are C(R⁴), X⁵ is N, R¹ is Cyclopropyl, R² is Hydrogen, and R³ isPyridin-3-yl A. Preparation ofN-(3-(1-cyclopropyl-1H-imidazol-5-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

Step 1: A solution of 3-(1,3-dioxolan-2-yl)aniline (3.26 g, 19.7 mmol),4-bromopicolinic acid (4.38 g, 21.7 mmol),(2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluroniumhexafluorophosphate (HATU) (8.99 g, 23.6 mmol), and N-methylmorpholine(2.6 mL, 23.6 mmol) in N,N-dimethylformamide was stirred at roomtemperature for 30 minutes. The solvent was removed under reducedpressure, and the residue was purified by flash chromatography (1:1Hexanes/ethyl acetate) to afford a mixture ofN-(3-(1,3-dioxolan-2-yl)phenyl)-4-bromopicolinamide acetal and thecorresponding aldehyde (5.56 g, ˜81% yield, contains ˜15% aldehyde).M+1=349.1

Step 2/3: To a solution of the product of Step (1.12 g, 3.23 mmol) inacetone/water (4:1, 0.2 M), was added 4-methylbenzenesulfonic acid (61mg, 0.323 mmol), and the mixture was stirred overnight. The reaction wasdiluted with methylene chloride and washed with brine (2×). The organicswere dried over magnesium sulfate, filtered and the solvent removed fromthe filtrate under reduced pressure, to provide a white solid. Thismaterial was dissolved in methylene chloride, (0.1 M), 4 Å powderedmolecular sieves (3.2 g, 1 g/mmol) and cyclopropyl amine (1.12 mL, 12.9mmol) were added and the reaction mixture was stirred for 6 hours. Themolecular sieves were filtered off, washed with methylene chloride andsolvent removed from the filtrate under reduced pressure, to afford 1.1g (quantitative yield) of4-promo-N-(3-((cyclopropylimino)methyl)phenyl)-picolinamide as a whitesolid. M+1=343.1.

Step 4: To a solution of4-bromo-N-(3-((cyclopropylimino)methyl)phenyl)-picolinamide (970 mg,2.83 mmol) in dimethoxyethane/methanol (2:1, 0.1M) were addedtoluenesulfonylmethyl isocyanide (1.10 g, 5.65 mmol) andcyclopropylamine (392 μL, 5.65 mmol). The reaction mixture was stirredfor 14 hours at 52° C., and additional toluenesulfonylmethyl isocyanide(550 mg, 2.83 mmol) was added. The reaction mixture was stirred anadditional 6 hours, the solvent removed under reduced pressure,concentrated, and the residue purified by flash chromatography (2-8%methanol in methylene chloride) to afford 110 mg of4-bromo-N-(3-(1-cyclopropyl-1H-imidazol-5-yl)phenyl)picolinamide.M+1=383.1

Step 5: A suspension of4-bromo-N-(3-(1-cyclopropyl-1H-imidazol-5-yl)phenyl)picolinamide (75.0mg, 0.196 mmol), boronic acid (33.8 mg, 0.274 mmol), dppf(Pd)Cl₂ (14.3mg, 0.0196), potassium carbonate (81.3 mg, 0.588 mmol) in degassedtoluene (1 mL), degassed water (0.5 mL) and degassed isopropanol (0.5mL) was heated at 95° C. for 2 hours. The aqueous phase was discardedand the solvent removed under reduced pressure from the organic portion.Purification by reverse phase HPLC providedN-(3-(1-cyclopropyl-1H-imidazol-5-yl)phenyl)-3,4′-bipyridine-2′-carboxamide(17.3 mg, 23%) as a white solid.

C₂₃H₁₉N₅O×HCO₂H. 382.0 (M+1). ¹H NMR (DMSO) d 10.83 (s, 1H), 9.11 (d,J=2 Hz, 1H), 8.86 (d, J=5 Hz, 1H), 8.72 (dd, J=2.5 Hz, 1H), 8.48 (d, J=1Hz, 1H), 8.48 (d, J=1 Hz, 1H), 8.32-8.36 (m, 1H), 8.27 (s, 1H), 8.20 (s,1H), 8.10 (dd, J=2, 5 Hz, 1H), 7.96 (d, J=8 Hz, 1H), 7.76 (s, 1H), 7.60(dd, J=5, 8 Hz, 1H), 7.46 (t, J=8 Hz, 1H), 7.41 (d, J=8 Hz), 3.57-3.61(m, 1H), 0.99-1.04 (m, 2H), 0.86-0.91 (m, 2H).

B. Similarly, following the procedure of Example 22A, but optionallyreplacing 3-(1,3-dioxolan-2-yl)aniline with other aromatic amines,optionally replacing 4-bromopicolinic acid with other acids, andoptionally replacing cyclopropylamine with other amines, the followingcompounds of Formula (I) were prepared:

4-(1H-benzo[d]imidazol-1-yl)-N-(3-(1-cyclopropyl-1H-imidazol-5-yl)phenyl)picolinamide

C₂₅H₂₀N₆O. 421.0 (M+1). ¹H NMR (DMSO) d 10.90 (s, 1H), 8.95 (d, J=5 Hz,1H), 8.91 (s, 1H), 8.48 (d, J=2 Hz, 1H), 8.28 (s, 1H), 8.13 (dd, J=2.5Hz, 1H), 7.97 (d, J=5 Hz, 1H), 7.89 (d, J=8 Hz, 1H), 7.84 (d, J=8 Hz,1H), 7.76 (s, 1H), 7.38-7.49 (m, 4H), 7.11 (s, 1H), 3.57-3.61 (m, 1H),0.98-1.04 (m, 2H), 0.86-0.91 (m, 2H).

6-cyclopropyl-N-(3-(1-cyclopropyl-1H-imidazol-5-yl)phenyl)-3,4′-bipyridine-2′-carboxamide

C₂₆H₂₃N₅O. 422.1 (M+1). ¹H NMR (CDCl₃) d 10.19 (s, 1H), 8.80 (d, J=2 Hz,1H), 8.68 (d, J=5 Hz, 1H), 8.49 (d, J=1 Hz, 1H), 8.31-8.33 (m, 1H), 8.22(br s, 1H), 7.89 (dd, J=2, 8 Hz, 1H), 7.70 (dd, J=2, 7 Hz, 1H), 7.66 (d,J=8 Hz, 1H), 7.49 (t, J=8 Hz, 1H), 7.66 (d, J=8 Hz, 1H), 7.27-7.31 (m,3H), 3.48-3.58 (m, 1H), 2.09-2.16 (m, 1H), 1.03-1.27 (m, 8H).

N-(3-(1-cyclopropyl-1H-imidazol-5-yl)phenyl)-4-(quinolin-3-yl)picolinamide

C₂₇H₂₁N₅O. 432.1 (M+1). ¹H NMR (CDCl₃) d 10.19 (s, 1H), 9.25 (d, J=2 Hz,1H), 8.76 (d, J=5 Hz, 1H), 8.66 (d, J=1 Hz, 1H), 8.53 (d, J=2 Hz, 1H),8.25-8.28 (m, 1H), 8.16 (d, J=8 Hz, 1H), 7.94 (d, J=8 Hz, 1H), 7.85-7.88(m, 2H), 7.80 (dt, J=3, 7, 8 Hz, 1H), 7.61-7.68 (m, 2H), 7.46 (t, J=8Hz, 1H), 7.32 (d, J=8 Hz, 1H), 7.20 (s, 1H), 3.48-3.53 (m, 1H),1.07-1.11 (m, 2H), 0.95-1.01 (m, 2H).

C. Similarly, following the procedure of Example 22A, but optionallyreplacing 3-(1,3-dioxolan-2-yl)aniline with other aromatic amines,optionally replacing 4-bromopicolinic acid with other acids, andoptionally replacing cyclopropylamine with other amines, other compoundsof Formula (I) are prepared.

EXAMPLE 23 Preparation of Compounds of Formula I A. Preparation ofN-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1-isopropyl-1H-pyrrolo[3,2-b]pyridin-6-yl)picolinamide

A suspension of 4-(1-isopropyl-1H-pyrrolo[3,2-b]pyridin-6-yl)picolinicacid (50 mg, 0.178 mmol), 3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)aniline(40 mg, 0.20 mmol), HATU (75 mg, 0.20 mmol) and diisopropylethylamine(0.06 mL, 0.35 mmol) in N,N-dimethylformamide (2 mL) was stirred at roomtemperature for 1 hour. The solvent was removed under reduced pressureand the residue was suspended and sonicated in 2:1 water:acetonitrile.The solid was isolated by filtration to giveN-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1-isopropyl-1H-pyrrolo[3,2-b]pyridin-6-yl)picolinamideas a white powder (HPF₆ salt, 75 mg, 90% yield). C₂₇H₂₅N₇O×HPF₆. 464.1(M+1). ¹H NMR (DMSO) d 11.01 (s, 1H), 9.22 (m, 2H), 8.92 (d, J=5.2 Hz,1H), 8.76 (s, 1H), 8.63 (s, 1H), 8.42 (d, J=3.2 Hz, 1H), 8.26 (m, 2H),8.10 (d, J=8.0 Hz, 1H), 7.71 (d, J=8.0 Hz, 1H), 7.58 (t, J=8.0 Hz, 1H),6.91 (d, J=3.2 Hz, 1H), 5.23 (sept, J=6.4 Hz, 1H), 3.69 (m, 1H), 1.56(d, J=6.4 Hz, 6H), 1.12 (m, 2H), 0.98 (m, 2H).

B. Similarly, following the procedure of Example 23A, but optionallyreplacing 4-(1-isopropyl-1H-pyrrolo[3,2-b]pyridin-6-yl)picolinic acidwith other compounds of formula (1), and optionally replacing3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)aniline with other compounds offormula (2), the following compounds of Formula (I) were prepared:

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(pyrazin-2-yl)picolinamide

C₂₁H₁₇N₇O. 384.1 (M+1). ¹H NMR (DMSO) d 10.98 (s, 1H), 9.53 (d, J=1.2Hz, 1H), 8.94 (d, J=5.2 Hz, 1H), 8.88 (m, 2H), 8.81 (d, J=2.4 Hz, 1H),8.63 (s, 1H), 8.60 (s, 1H), 8.43 (dd, J=5.2, 2.0 Hz, 1H), 8.08 (d, J=9.2Hz, 1H), 7.70 (d, J=8.0 Hz, 1H), 7.56 (t, J=8.0 Hz, 1H), 3.66 (m, 1H),1.08 (m, 2H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(2-hydroxypropan-2-yl)-3,4′-bipyridine-2′-carboxamide

C₂₅H₂₄N₆O₂. 441.1 (M+1). ¹H NMR (DMSO) d 10.95 (s, 1H), 9.01 (d, J=1.6Hz, 1H), 8.85 (d, J=5.2 Hz, 1H), 8.63 (s, 1H), 8.59 (s, 1H), 8.47 (d,J=1.2 Hz, 1H), 8.32 (dd, J=8.4, 2.4 Hz, 1H), 8.01 (m, 2H), 7.84 (d,J=8.4 Hz, 1H), 7.69 (d, J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 5.38 (br,1H), 3.67 (m, 1H), 1.50 (s, 6H), 1.08 (m, 2H), 0.95 (m, 2H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-6-(2-hydroxypropan-2-yl)-3,4′-bipyridine-2′-carboxamide

C₂₄H₂₃N₇O₂. 442.1 (M+1). ¹H NMR (DMSO) d 10.70 (s, 1H), 9.03 (d, J=1.6Hz, 1H), 8.86 (d, J=5.6 Hz, 1H), 8.70 (s, 1H), 8.53 (d, J=1.2 hz, 1H),8.41 (d, J=7.6 Hz, 1H), 8.34 (dd, J=8.0, 2.4 Hz, 1H), 8.14 (m, 2H), 7.89(d, J=6.8 Hz, 1H), 7.84 (d, J=8.4 Hz, 1H), 5.38 (s, 1H), 4.11 (m, 1H),1.49 (s, 6H), 1.04 (m, 4H).

N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(2,2,2-trifluoro-1-methoxyethyl)-1H-imidazol-1-yl)benzamide

C₂₃H₂₀F₃N₇O₂×HPF₆. 484.1 (M+1). ¹H NMR (DMSO) d 10.93 (s, 1H), 8.78 (s,1H), 8.59 (s, 1H), 8.28 (m, 2H), 8.07 (m, 2H), 7.97 (m, 2H), 7.82 (d,J=8.0 Hz, 1H), 7.72 (t, 8.0 Hz, 1H), 5.02 (q, J=7.2 Hz, 1H), 4.25 (m,1H), 3.41 (s, 3H), 0.99 (m, 4H). ¹⁹F NMR (DMSO) d −70.20 (d, J=710 Hz,HPF₆), −74.79 (d, J=7.2 Hz, 3F).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1-(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-b]pyridin-6-yl)picolinamide

C₂₆H₂₀F₃N₇O×HPF₆. 504.1 (M+1). ¹H NMR (DMSO) d 11.02 (s, 1H), 9.11 (s,1H), 9.02 (s, 1H), 8.90 (d, J=5.2 Hz, 1H), 8.86 (s, 2H), 8.63 (s, 1H),8.18 (dd, J=8.8, 2.0 Hz, 1H), 8.12 (d, J=8.8 Hz, 1H), 8.04 (d, J=3.2 Hz,1H), 7.71 (d, J=8.0 Hz, 1H), 7.59 (t, J=8.0 Hz, 1H), 6.89 (d, J=3.2 Hz,1H), 5.49 (q, J=8.8 Hz, 1H), 3.71 (m, 1H), 1.10 (m, 2H), 0.99 (m, 2H).¹⁹F NMR (DMSO) d −70.20 (d, J=710 Hz, HPF₆), −70.38 (t, J=8.8 Hz, 3F).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(2,2,2-trifluoroethyl)-3,4′-bipyridine-2′-carboxamide

C₂₄H₁₉F₃N₆O. 465.1 (M+1). ¹H NMR (DMSO) d 10.98 (s, 1H), 9.12 (d, J=2.4Hz, 1H), 8.88 (d, J=5.6 Hz, 1H), 8.64 (s, 1H), 8.59 (s, 1H), 8.50 (s,1H), 8.40 (dd, J=4.4, 2.4 Hz, 1H), 8.11 (m, 2H), 7.69 (m, 2H), 7.57 (t,J=8.0 Hz, 1H), 3.95 (q, J=11.6 Hz, 2H), 3.67 (m, 1H), 1.08 (m, 2H), 0.94(m, 2H). ¹⁹F NMR (DMSO) d −62.91 (t, J=11.6 Hz, 3F).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)picolinamide

C₂₅H₂₃N₇O×HCl. 438.1 (M+1). ¹H NMR (DMSO) d 11.11 (s, 1H), 9.97 (br,2H), 9.56 (s, 1H), 9.10 (s, 1H), 8.90 (d, J=5.2 Hz, 1H), 8.70 (s, 1H),8.54 (s, 1H), 8.45 (s, 1H), 8.17 (m, 2H), 7.75 (d, J=8.0 Hz, 1H), 7.65(t, J=8.0 Hz, 1H), 4.44 (m, 2H), 3.83 (m, 1H), 3.52 (m, 2H), 3.26 (m,2H), 1.12 (m, 4H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(6-(2,2,2-trifluoroethyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)picolinamide

C₂₇H₂₄F₃N₇O. 520.1 (M+1). ¹H NMR (DMSO) d 10.94 (s, 1H), 8.90 (d, J=2.0Hz, 1H), 8.84 (d, J=5.2 Hz, 1H), 8.63 (s, 1H), 8.59 (s, 1H), 8.48 (d,J=1.2 Hz, 1H), 8.08 (m, 3H), 7.79 (d, J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz,1H), 3.98 (s, 2H), 3.66 (m, 1H), 3.44 (q, J=10.4 Hz, 2H), 3.09 (m, 2H),2.99 (m, 2H), 1.08 (m, 2H), 0.95 (m, 2H). ¹⁹F NMR (DMSO) d −68.2 (t,J=10.4 Hz, 3F).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(6-isopropyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)picolinamide

C₂₈H₂₉N₇O. 480.1 (M+1). ¹H NMR (DMSO) d 10.96 (s, 1H), 8.87 (s, 1H),8.84 (d, J=4.8 Hz, 1H), 8.63 (s, 1H), 8.60 (s, 1H), 8.47 (s, 1H), 8.07(m, 3H), 7.69 (d, J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz, 1H), 3.81 (m, 1H),3.67 (m, 1H), 2.96 (m, 4H), 2.87 (m, 2H), 1.09 (m, 8H), 0.95 (m, 2H).

N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(6-methyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)picolinamide

C₂₆H₂₅N₇O. 452.1 (M+1). ¹H NMR (DMSO) d 10.96 (s, 1H), 8.88 (d, J=2.0Hz, 1H), 8.84 (d, J=5.6 Hz. 1H), 8.63 (s, 1H), 8.59 (s, 1H), 8.47 (d,J=0.8 Hz, 1H), 8.08 (m, 3H), 7.69 (d, J=8.0 Hz, 1H), 7.55 (t, J=8.0 Hz,1H), 3.67 (m, 3H), 2.98 (m, 2H), 2.77 (m, 2H), 2.41 (s, 3H), 1.08 (m,2H), 0.95 (m, 2H).

C. Similarly, following the procedure of Example 23A, but optionallyreplacing 4-(1-isopropyl-1H-pyrrolo[3,2-b]pyridin-6-yl)picolinic acidwith other compounds of formula (1), and optionally replacing3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)aniline with other compounds offormula (2), other compounds of Formula (I) are prepared.

EXAMPLE 24 Biological Assays

ASK1 (Apoptosis Signal-Regulating Kinase 1) TR-FRET Kinase Assay(Biochemical IC₅₀)

The ability of compounds to inhibit ASK1 kinase activity was determinedusing a time resolved fluorescence resonance energy transfer [TR-FRET]assay utilizing biotinylated myelin basic protein [biotin-MBP] as theprotein substrate. A Beckman Biomek FX liquid handling robot wasutilized to spot 2 μL/well of compounds in 2.44% aqueous DMSO into lowvolume 384-well polypropylene plates [Nune, #267460] to give a finalconcentration of between 100 μM and 0.5 nM compound in the kinase assay.A Decrac Fluidics Equator was used to dispense 3 μL/well of 0.667 ng/μL[Upstate Biotechnologies, #14-606, or the equivalent protein preparedin-house] and 0.1665 ng/mL biotin-MBP [Upstate Biotechnologies, #13-111]in buffer (85 mM MOPS, pH 7.0, 8.5 mM Mg-acetate, 5% glycerol, 0.085%NP-40, 1.7 mM DTT and 1.7 mg/mL BSA) into the plates containing thespotted compounds. The enzyme was allowed to pre-incubate with compoundfor 20 minutes prior to initiating the kinase reaction with the additionof 5 μL/well 300 μM ATP in buffer (50 mM MOPS, pH 7.0, 5 mM Mg-acetate,1 mM DTT, 5% DMSO) using the Decrac Fluidics Equator. The kinasereactions were allowed to proceed for 20 minutes at ambient temperatureand were subsequently stopped with the addition of 5 μL/well 25 mM EDTAusing the Deerac Fluidics Equator. The Biomek FX was then used totransfer 1 μL/well of each completed kinase reaction to the wells of anOptiPlate-1536 white polystyrene plate [PerkinElmer, #6004299] thatcontained 5 μL/well detection reagents (1.11 nM Eu-W1024 labeledanti-phosphothreonine antibody [PerkinElmer, #AD0094] and 55.56 nMstreptavidin allophycocyanin [PerkinElmer, #CR130-100] in 1×LANCEdetection buffer [PerkinElmer, #CR97-100]). The TR-FRET signal was thenread on a Perkin. Elmer Envision plate reader after incubating theplates at ambient temperature for 2 hours. The 100% inhibition positivecontrol wells were generated by switching the order of addition of theEDTA and ATP solutions described above. These wells and 0% inhibitionwells containing spots of 2.44% DMSO at the beginning of the assay wereused in calculating the % inhibition for the test compounds. When testedby the above method, the compounds of Formula (I) inhibited ASK1. Forexample;

IC₅₀ No. Compound (nM) 15-(2,5-difluorophenyl)-N-(3-(4-methyl-4H-1,2,4-triazol- 391493-yl)phenyl)nicotinamide 2N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-5- 5587 phenylnicotinamide3 2-hydroxy-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-6-phenylpyrimidine-4-carboxamide 4N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 701 phenylpicolinamide 5N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-6- phenylpicolinamide 6N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-2,3′-bipyridine-6-carboxamide 7N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(quinolin-6-yl)picolinamide 8N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-3,3′- 220bipyridine-5-carboxamide 9N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′- 42bipyridine-2′-carboxamide 10N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-2- 4821phenylisonicotinamide 11 5-methoxy-N-(3-(4-methyl-4H-1,2,4-triazol-3- 40yl)phenyl)-3,4′-bipyridine-2′-carboxamide 125-acetamido-N-(3-(4-methyl-4H-1,2,4-triazol-3- 101yl)phenyl)-3,4′-bipyridine-2′-carboxamide 134-(imidazo[1,2-a]pyridin-3-yl)-N-(3-(4-methyl-4H- 441,2,4-triazol-3-yl)phenyl)picolinamide 14N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 279phenylpicolinamide 15N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′- 11bipyridine-2′-carboxamide 16N-(3-(4-(3-amino-3-oxopropyl)-4H-1,2,4-triazol-3- 114yl)phenyl)-3,4′-bipyridine-2′-carboxamide 17N-(3-(4-(2-acetamidoethyl)-4H-1,2,4-triazol-3- 73yl)phenyl)-3,4′-bipyridine-2′-carboxamide 184-(1-methyl-1H-imidazol-5-yl)-N-(3-(4-methyl-4H- 391,2,4-triazol-3-yl)phenyl)picolinamide 19(R)-N-(3-(4-(1-hydroxypropan-2-yl)-4H-1,2,4-triazol-3- 9yl)phenyl)-3,4′-bipyridine-2′-carboxamide 20(S)-N-(3-(4-(1-hydroxypropan-2-yl)-4H-1,2,4-triazol-3- 39yl)phenyl)-3,4′-bipyridine-2′-carboxamide 21N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 12methoxy-3,4′-bipyridine-2′-carboxamide 226-amino-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 9yl)phenyl)-3,4′-bipyridine-2′-carboxamide 23 methyl2′-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 167yl)phenylcarbamoyl)-3,4′-bipyridin-6-ylcarbamate 24N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 21(pyrimidin-5-yl)picolinamide 254-(2-aminopyrimidin-5-yl)-N-(3-(4-cyclopropyl-4H- 131,2,4-triazol-3-yl)phenyl)picolinamide 26N-(3-(4-(tetrahydro-2H-pyran-4-yl)-4H-1,2,4-triazol-3- 1967yl)phenyl)-3,4′-bipyridine-2′-carboxamide 27N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 11(1H-imidazol-1-yl)picolinamide 28N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 110(1H-1,2,4-triazol-1-yl)picolinamide 29N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4- 443methylpiperazin-1-yl)picolinamide 30N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 335morpholinopicolinamide 31N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 63hydroxy-3,4′-bipyridine-2′-carboxamide 32N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(3- 569oxopiperazin-1-yl)picolinamide 334-(3-aminopyrrolidin-1-yl)-N-(3-(4-methyl-4H-1,2,4- 3483triazol-3-yl)phenyl)picolinamide 34(R)-N-(3-(4-(2-hydroxypropyl)-4H-1,2,4-triazol-3- 195yl)phenyl)-3,4′-bipyridine-2′-carboxamide 35(S)-N-(3-(4-(2-hydroxypropyl)-4H-1,2,4-triazol-3- 87yl)phenyl)-3,4′-bipyridine-2′-carboxamide 36N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1- 18methyl-1H-imidazol-5-yl)picolinamide 374-(1H-benzo[d]imidazol-1-yl)-N-(3-(4-cyclopropyl-4H- 81,2,4-triazol-3-yl)phenyl)picolinamide 38N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4- 17phenyl-1H-imidazol-1-yl)picolinamide 39N-(3-(4-cyclobutyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′- 63bipyridine-2′-carboxamide 40N-(3-(4-cyclopentyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′- 75bipyridine-2′-carboxamide 41N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(2- 48methyl-1H-imidazol-1-yl)picolinamide 42N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4- 11methyl-1H-imidazol-1-yl)picolinamide 43N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 8(4,5-dimethyl-1H-imidazol-1-yl)picolinamide 44N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4- 27(trifluoromethyl)-1H-imidazol-1-yl)picolinamide 45N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(2- 9methoxypyrimidin-5-yl)picolinamide 466′-methyl-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)- 2123,4′-bipyridine-2′-carboxamide 47N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 32(pyrrolidin-1-yl)-3,4′-bipyridine-2′-carboxamide 48N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 37fluoro-5-methyl-3,4′-bipyridine-2′-carboxamide 49N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 8(2,4-dimethoxypyrimidin-5-yl)picolinamide 506-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 8yl)phenyl)-3,4′-bipyridine-2′-carboxamide 51N2′-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)- 83,4′-bipyridine-2′,6-dicarboxamide 52N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 12(trifluoromethyl)-3,4′-bipyridine-2′-carboxamide 53N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 11methyl-3,4′-bipyridine-2′-carboxamide 54N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 53,4′-bipyridine-2′-carboxamide 55N-(3-(4-((1S,2S)-2-methylcyclopropyl)-4H-1,2,4- 24triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide 56N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 69(2,2,2-trifluoroethoxy)-3,4′-bipyridine-2′-carboxamide 57N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 244methyl-3,4′-bipyridine-2′-carboxamide 58N-(3-(4-(2,2,2-trifluoroethyl)-4H-1,2,4-triazol-3- 290yl)phenyl)-3,4′-bipyridine-2′-carboxamide 59N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5- 44(trifluoromethyl)-3,4′-bipyridine-2′-carboxamide 60N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5- 23fluoro-3,4′-bipyridine-2′-carboxamide 61N-(3-(4-((1-hydroxycyclopropyl)methyl)-4H-1,2,4- 174triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide 62(R)-N-(3-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4- 1237triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide 63(S)-N-(3-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4- 21triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide 64N2′-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)- 173,4′-bipyridine-2′,5-dicarboxamide 655-cyano-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 30yl)phenyl)-3,4′-bipyridine-2′-carboxamide 662-amino-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 86yl)phenyl)-3,4′-bipyridine-2′-carboxamide 67N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-2- 60methoxy-3,4′-bipyridine-2′-carboxamide 68N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1- 39methyl-1H-pyrazol-4-yl)picolinamide 69N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 11(imidazo[1,2-a]pyridin-3-yl)picolinamide 706-Chloro-[3,2′:5′,4′]terpyridine-2″-carboxylic acid [3-(4- 106cyclopropyl-4H-[1,2,4]triazol-3-yl)-phenyl]-amide 71N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5- 17methoxy-3,4′-bipyridine-2′-carboxamide 72N-(3-(1-cyclopropyl-1H-imidazol-5-yl)phenyl)-3,4′- 36bipyridine-2′-carboxamide 73N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 11(1,2-dimethyl-1H-imidazol-5-yl)picolinamide 74N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-2- 79methyl-3,4′-bipyridine-2′-carboxamide 75N5-tert-butyl-N2′-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 10yl)phenyl)-3,4′-bipyridirie-2′,5-dicarboxamide 765-chloro-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 34yl)phenyl)-3,4′-bipyridine-2′-carboxamide 77N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(3- 79(methylsulfonyl)phenyl)picolinamide 78N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(2- 572(methylsulfonyl)phenyl)picolinamide 79N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4- 6(methylsulfonyl)phenyl)picolinamide 80N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 36(pyridin-3-yl)quinoline-2-carboxamide 81N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 16(1H-imidazo[4,5-b]pyridin-1-yl)picolinamide 82N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 20(3H-imidazo[4,5-b]pyridin-3-yl)picolinamide 83N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 53(1H-imidazo[4,5-c]pyridin-1-yl)picolinamide 84N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 13(quinolin-3-yl)picolinamide 854-(1H-benzo[d][1,2,3]triazol-1-yl)-N-(3-(4-cyclopropyl- 1414H-1,2,4-triazol-3-yl)phenyl)picolinamide 86N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 9(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-1- yl)picolinamide 87N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 69(pyrazin-2-yl)picolinamide 884-(1H-benzo[d]imidazol-1-yl)-N-(3-(1-cyclopropyl-1H- 35imidazol-5-yl)phenyl)picolinamide 89N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 26(isoquinolin-4-yl)picolinamide 90N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 38(1,5-dimethyl-1H-pyrazol-4-yl)picolinamide 91N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 18(dimethylamino)-3,4′-bipyridine-2′-carboxamide 92N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 13(1H-pyrrolo[2,3-b]pyridin-5-yl)picolinamide 93N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 43fluoro-3,4′-bipyridine-2′-carboxamide 94N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 61isopropoxy-3,4′-bipyridine-2′-carboxamide 956-cyclobutoxy-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 31yl)phenyl)-3,4′-bipyridine-2′-carboxamide 96N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4- 13(N-cyclopropylsulfamoyl)phenyl)picolinamide 97N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4- 81sulfamoylphenyl)picolinamide 98N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4- 7(N-methylsulfamoyl)phenyl)picolinamide 99N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4- 17(N-isopropylsulfamoyl)phenyl)picolinamide 1006-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3- 6yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide 101N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 74-(4-(methylsulfonyl)phenyl)picolinamide 102N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 9isopropyl-3,4′-bipyridine-2′-carboxamide 1036-cyclobutyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 11yl)phenyl)-3,4′-bipyridine-2′-carboxamide 1046-cyclopropoxy-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 12yl)phenyl)-3,4′-bipyridine-2′-carboxamide 105N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4- 15(2-oxoimidazolidin-1-yl)phenyl)picolinamide 106N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 8ethyl-3,4′-bipyridine-2′-carboxamide 1076-cyclopropyl-N-(3-(1-cyclopropyl-1H-imidazol-5- 31yl)phenyl)-3,4′-bipyridine-2′-carboxamide 108N-(3-(1-cyclopropyl-1H-imidazol-5-yl)phenyl)-4- 41(quinolin-3-yl)picolinamide 1096-cyclopentyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 21yl)phenyl)-3,4′-bipyridine-2′-carboxamide 110N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(1- 8methyl-2-oxopyrrolidin-3-yl)-3,4′-bipyridine-2′- carboxamide 111N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 94-(4-(N-methylsulfamoyl)phenyl)picolinamide 112N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 144-(quinolin-3-yl)picolinamide 113N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 104-(4-phenyl-1H-imidazol-1-yl)picolinamide 114N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 5propyl-3,4′-bipyridine-2′-carboxamide 115N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 15neopentyl-3,4′-bipyridine-2′-carboxamide 116N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1- 23methyl-2-phenyl-1H-imidazol-5-yl)picolinamide 117N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4- 12(ethylsulfonyl)phenyl)picolinamide 118N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4- 9(isopropylsulfonyl)phenyl)picolinamide 119N-(3-(4-cyclopropyl-4H-1,2,4-triazo1-3-yl)phenyl)-6- 9(ethylamino)-3,4′-bipyridine-2′-carboxamide 120N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 6(cyclopropylamino)-3,4′-bipyridine-2′-carboxamide 121N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 47(imidazo[2,1-b][1,3,4]thiadiazol-5-yl)picolinamide 1224-(4-chloro-1H-imidazol-1-yl)-N-(3-(4-cyclopropyl-4H- 171,2,4-triazol-3-yl)phenyl)picolinamide 123N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(2- 10cyclopropylpyrimidin-5-yl)picolinamide 124N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6′- 422(trifluoromethyl)-3,4′-bipyridine-2′-carboxamide 125N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 1453(quinolin-3-yl)-6-(trifluoromethyl)picolinamide 126N-(6-(1-cyclopropyl-1H-imidazol-5-yl)pyridin-2-yl)-4- 1038(quinolin-3-yl)picolinamide 1276-cyclopropyl-N-(6-(1-cyclopropyl-1H-imidazol-5- 211yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide 128N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 6(1H-pyrrolo[3,2-b]pyridin-6-yl)picolinamide 129N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4- 22cyclopropylphenyl)picolinamide 130N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 123-(pyridin-3-yl)benzamide 131N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 11(methylthio)-3,4′-bipyridine-2′-carboxamide 132N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 150(isobutylthio)-3,4′-bipyridine-2′-carboxamide 133N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(5- 10cyclopropylpyrazin-2-yl)picolinamide 1346-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 34yl)phenyl)-5-fluoro-3,4′-bipyridine-2′-carboxamide 1355-chloro-6-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4- 131triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide 136N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(2- 7methoxyethylamino)-3,4′-bipyridine-2′-carboxamide 137N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4- 31(methylsulfonyl)piperazin-1-yl)picolinamide 138N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 8ethyl-5-fluoro-3,4′-bipyridine-2′-carboxamide 1395-chloro-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 16yl)phenyl)-6-ethyl-3,4′-bipyridine-2′-carboxamide 1404-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4- 9cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide 141N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5,6- 13diethyl-3,4′-bipyridine-2′-carboxamide 142N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 11(furo[3,2-b]pyridin-6-yl)picolinamide 143N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(3- 15methyl-3H-imidazo[4,5-b]pyridin-6-yl)picolinamide 144N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(6- 14cyclopropylpyridin-3-yl)pyrimidine-4-carboxamide 145N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(2- 7ethylpyrimidin-5-yl)picolinamide 146N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5- 8ethyl-3,4′-bipyridine-2′-carboxamide 1476-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 400yl)-4-fluorophenyl)-3,4′-bipyridine-2′-carboxamide 148N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)-4- 56fluorophenyl)-6-ethyl-3,4′-bipyridine-2′-carboxamide 1496-tert-butyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 25yl)phenyl)-3,4′-bipyridine-2′-carboxamide 150N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 173-(quinolin-3-yl)benzamide 151N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 83-(6-cyclopropylpyridin-3-yl)benzamide 1526-cyclopropyl-N-(2-(4-cyclopropyl-4H-1,2,4-triazol-3- 286yl)pyridin-4-yl)-3,4′-bipyridine-2′-carboxamide 153N-(2-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-4-yl)- 4094-(quinolin-3-yl)picolinamide 154N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 34(5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)picolinamide 1556-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 10yl)-2-fluorophenyl)-3,4′-bipyridine-2′-carboxamide 1565-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 11yl)phenyl)-3,4′-bipyridine-2′-carboxamide 157N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)-2- 38fluorophenyl)-3,4′-bipyridine-2′-carboxamide 158N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4- 5ethyl-1H-imidazol-1-yl)picolinamide 159N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 34-(4-methyl-1H-imidazol-1-yl)picolinamide 160N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 44-(4,5-dimethyl-1H-imidazol-1-yl)picolinamide 161N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(6- 9(2,2,2-trifluoroethyl)-5,6,7,8-tetrahydro-1,6-naphthyridin-3-yl)picolinamide 1626-cyclopropyl-N-(4-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide 163N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4- 4isopropyl-1H-imidazol-1-yl)picolinamide 164N-(4-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 183,4′-bipyridine-2′-carboxamide 165N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(2- 5hydroxypropan-2-yl)-3,4′-bipyridine-2′-carboxamide 166N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 56-(2-hydroxypropan-2-yl)-3,4′-bipyridine-2′- carboxamide 167N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 74-(4-isopropyl-1H-imidazol-1-yl)picolinamide 1686-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 143yl)-5-fluorophenyl)-3,4′-bipyridine-2′-carboxamide 169N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)-5- 157fluorophenyl)-3,4′-bipyridine-2′-carboxamide 1704-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4- 7cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2- yl)picolinamide 171N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 7(2,2,2-trifluoroethyl)-3,4′-bipyridine-2′-carboxamide 172N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(6- 17isopropyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3- yl)picolinamide 173N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(6- 21methyl-5,6,7,8-tetrahydro-1,6-naphthyridin-3- yl)picolinamide 174N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(3- 93hydroxypiperidin-1-yl)picolinamide 175N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 104-(3-hydroxypiperidin-1-yl)picolinamide 1766-cyclopropyl-N-(6-(4-isopropyl-4H-1,2,4-triazol-3- 13yl)pyridin-2-yl)-3,4′-bipyridine-2′-carboxamide 177N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4- 47ethyl-3-oxopiperazin-1-yl)picolinamide 178N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 74-(4-ethyl-3-oxopiperazin-1-yl)picolinamide 179(S)-6-cyclopropyl-N-(6-(4-(1,1,1-trifluoropropan-2-yl)- 194H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′- carboxamide 180N-(3-(4-isopropyl-4H-1,2,4-triazol-3-yl)phenyl)-3,4′- 27bipyridine-2′-carboxamide 181N-(3-(4-(cyclopropylmethyl)-4H-1,2,4-triazol-3- 131yl)phenyl)-3,4′-bipyridine-2′-carboxamide 1824-(4-cyclopropyl-2-methyl-1H-imidazol-1-yl)-N-(3-(4- 15cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide 1834-(4-cyclopropyl-2-methyl-1H-imidazol-1-yl)-N-(6-(4- 8cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2- yl)picolinamide 1844-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-isopropyl- 204H-1,2,4-triazol-3-yl)phenyl)picolinamide 1854-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4- 34(cyclopropylmethyl)-4H-1,2,4-triazol-3- yl)phenyl)picolinamde 1864-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(1- 30phenylethyl)-4H-1,2,4-triazol-3-yl)phenyl)picolinamide 187N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 44-(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-1- yl)picolinamide 188N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 64-(4-(trifluoromethyl)-1H-imidazol-1-yl)picolinamide 189(S)-4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(1,1,1- 9trifluoropropan-2-yl)-4H-1,2,4-triazol-3- yl)phenyl)picolinamide 190N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4- 13(1,5-naphthyridin-3-yl)picolinamide 191N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 183-(1,5-naphthyridin-3-yl)benzamide 1923-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4- 7cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2- yl)benzamide 193N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 53-(4-isopropyl-1H-imidazol-1-yl)benzamide 194N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4- 12(trifluoromethyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-1-yl)picolinamide 195N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 84-(4-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-1-yl)picolinamide 1963-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4- 1257cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- methylbenzamide 1975-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4- 47cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2- methylbenzamide 198N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4- 19(perfluoroethyl)-1H-imidazol-1-yl)picolinamide 199N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 94-(4-(perfluoroethyl)-1H-imidazol-1-yl)picolinamide 2003-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4- 11cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-y1)-4- methylbenzamide 2014-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-N-(6-(4- 14cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2- yl)picolinamide 2024-(3-cyclopropyl-1H-1,2,4-triazol-1-yl)-N-(3-(4- 17cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide 2034-(5-cyclopropyl-1H-1,2,4-triazol-1-yl)-N-(3-(4- 538cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide 204N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 173-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)benzamide 2053-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4- 9cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5- fluorobenzamide 206N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(4- 9(2,2,2-trifluoro-1-hydroxyethyl)-1H-imidazol-1- yl)picolinamide 207N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 114-(4-(2,2,2-trifluoro-1-hydroxyethyl)-1H-imidazol-1- yl)picolinamide 208N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 53-(4-(2,2,2-trifluoro-1-hydroxyethyl)-1H-imidazol-1- yl)benzamide 2093-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4- 7cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5- methylbenzamide 2103-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4- 7cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5- methylbenzamide 211N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 93-(4,5-dimethyl-1H-imidazol-1-yl)benzamide 212N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 93-(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-1- yl)benzamide 2131-(3-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2- 11ylcarbamoyl)phenyl)-5-methyl-1H-imidazole-4- carboxylic acid 214(S)-3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-(1- 159phenylethyl)-4H-1,2,4-triazol-3-yl)pyridin-2- yl)benzamide 2156-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3- 30yl)pyridin-2-yl)-5′-methyl-3,4′-bipyridine-2′- carboxamide 216(S)-3-(4,5-dimethyl-1H-imidazol-1-yl)-N-(6-(4-(1,1,1- 8trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2- yl)benzamide 217(S)-3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-(1- 14phenylethyl)-4H-1,2,4-triazol-3-yl)pyridin-2- yl)benzamide 2183-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-isopropyl- 54H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide 2196-cyclopropyl-N-(3-(4-isopropyl-4H-1,2,4-triazol-3- 16yl)phenyl)-3,4′-bipyridine-2′-carboxamide 220(S)-6-cyclopropyl-N-(3-(4-(1-phenylethyl)-4H-1,2,4- 61triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide 221N-(3-(4-cyclobutyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 31cyclopropyl-3,4′-bipyridine-2′-carboxamide 222 (S)-tert-butyl2-(3-(3-(6-cyclopropyl-3,4′-bipyridine-2′- 79carboxamido)phenyl)-4H-1,2,4-triazol-4-yl)propanoate 223(S)-6-cyclopropyl-N-(3-(4-(1,1,1-trifluoropropan-2-yl)- 454H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′- carboxamide 224N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 135-(6-cyclopropylpyridin-3-yl)-2-fluorobenzamide 225N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 1034-(6-cyclopropylpyridin-3-yl)quinoline-2-carboxamide 2264-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4- 16cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2- yl)quinoline-2-carboxamide227 4-chloro-3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4- 8cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2- yl)benzamide 2283-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4- 7cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4- methoxybenzamide 229N-(3-(4-sec-butyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 101cyclopropyl-3,4′-bipyridine-2′-carboxamide 230(S)-6-cyclopropyl-N-(3-(4-(1-cyclopropylethyl)-4H- 581,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′- carboxamide 2316-cyclopropyl-N-(3-(4-(pentan-3-yl)-4H-1,2,4-triazol-3- 1423yl)phenyl)-3,4′-bipyridine-2′-carboxamide 232(S)-6-cyclopropyl-N-(3-(4-(1-methoxypropan-2-yl)-4H- 171,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′- carboxamide 2336-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3- 14yl)pyridin-2-yl)-6′-methyl-3,4′-bipyridine-2′- carboxamide 234(S)-6-cyclopropyl-N-(6-(4-(1-methoxypropan-2-yl)-4H- 81,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′- carboxamide 235N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 153-(4-(2,2,2-trifluoro-1-methoxyethyl)-1H-imidazol-1- yl)benzamide 236N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 1394-(6-cyclopropylpyridin-3-yl)-7,8-dimethylquinoline-2- carboxamide 237(S)-N-(3-(4-sec-butyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 38cyclopropyl-3,4′-bipyridine-2′-carboxamide 238(S)-6-cyclopropyl-N-(3-(4-(3-methylbutan-2-yl)-4H- 61,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′- carboxamide 239(S)-6-cyclopropyl-N-(3-(4-(1-(2,6- 10929dimethylphenoxy)propan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide 240N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(6- 222cyclopropylpyridin-3-yl)-7,8-dimethylquinoline-2- carboxamide 2416-cyclopropyl-N-(6-(4-(1-methylpiperidin-4-yl)-4H- 6161,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′- carboxamide 242(S)-6-cyclopropyl-N-(3-(4-(3,3-dimethylbutan-2-yl)-4H- 11291,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′- carboxamide 243N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1- 15isopropyl-1H-pyrrolo[3,2-b]pyridin-6-yl)picolinamide 244N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(1- 25(2,2,2-trifluoroethyl)-1H-pyrrolo[3,2-b]pyridin-6- yl)picolinamide 2456-cyclopropyl-N-(6-(4-(1-(pyrrolidin-1-yl)propan-2-yl)- 364H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′- carboxamide 2466-cyclopropyl-N-(6-(4-((2S,3S)-3-hydroxybutan-2-yl)- 64H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′- carboxamide 2476-cyclopropyl-N-(6-(4-((2S,3R)-3-hydroxybutan-2-yl)- 104H-1,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′- carboxamide 2486-cyclopropyl-N-(6-(4-((2R)-3-hydroxybutan-2-yl)-4H- 71,2,4-triazol-3-yl)pyridin-2-yl)-3,4′-bipyridine-2′- carboxamide 2496-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 71yl)phenyl)-6′-methyl-3,4′-bipyridine-2′-carboxamide 2506-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 8yl)phenyl)-5′-methyl-3,4′-bipyridine-2′-carboxamide 251N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(6- 7methoxyquinolin-3-yl)picolinamide 252N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(5- 3412(1-hydroxyethyl)-1,3,4-oxadiazol-2-yl)picolinamide 253N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(3- 3489methyl-1,2,4-oxadiazol-5-yl)picolinamide 2544-(3-cyclopropyl-1,2,4-oxadiazol-5-yl)-N-(3-(4- 1269cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide 2554-(5-cyclopropyl-4-methyl-4H-1,2,4-triazol-3-yl)-N-(3- 685(4-cyclopropyl-4H-1,2,4-triazol-3- yl)phenyl)picolinamide 256N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)- 44-(5-methyl-4-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-1-yl)picolinamide 257N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-4-(5- 6methyl-4-(trifluoromethyl)-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-1-yl)picolinamide 2586′-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3- 852yl)pyridin-2-yl)-2,3′-bipyridine-6-carboxamide 2596′-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3- 8yl)pyridin-2-yl)-3,3′-bipyridine-5-carboxamide 2606′-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3- 30yl)pyridin-2-yl)-2,3′-bipyridine-4-carboxamide 261N-(6-(4-cyclopropyl-4H-1,2,4-triarol-3-yl)pyridin-2-yl)-5-(6-cyclopropylpyridin-3-yl)-2,4-difluorobenzamide 2626′-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-2,3′-bipyridine-4-carboxamide 2636′-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3- 3600yl)phenyl)-2,3′-bipyridine-6-carboxamide 264(S)-4-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4-(3- 23methylbutan-2-yl)-4H-1,2,4-triazol-3- yl)phenyl)picolinamide 2654-chloro-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3- 27yl)pyridin-2-yl)-5-(6-cyclopropylpyridin-3-yl)-2- fluorobenzamide 2666-cyclopropyl-N-(3-(4-(3-hydroxybutan-2-yl)-4H-1,2,4-triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide 2676-cyclopropyl-N-(3-(4-(2-phenylcyclopropyl)-4H-1,2,4- 425triazol-3-yl)phenyl)-3,4′-bipyridine-2′-carboxamide 268N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6- 13(cyclopropylmethyl)-3,4′-bipyridine-2′-carboxamide 2693-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)-N-(6-(4- 23cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2- yl)benzamide 2704-(5-cyclopropyl-1,3,4-thiadiazol-2-yl)-N-(3-(4- 107cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)picolinamide 271N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-5-(6- 24cyclopropylpyridin-3-yl)-2-methoxybenzamide 2725-(4-cyclopropyl-1H-imidazol-1-yl)-N-(3-(4- 11cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-2- methoxybenzamide

What is claimed is:
 1. A compound of formula (I)

wherein: R¹ is alkyl of 1-10 carbon atoms, cycloalkyl of 3-8 carbonatoms, alkenyl of 2-10 carbon atoms, alkynyl of 2-10 carbon atoms, aryl,heteroaryl or heterocyclyl, all of which are optionally substituted with1, 2, or 3 substituents selected from halo, oxo, alkyl of 1-6 carbonatoms, cycloalkyl of 3-8 carbon atoms, heterocyclyl, phenyl, phenoxy,halo, —CN, —O—R⁶, —C(O)—R⁶, —OC(O)—R⁶, —C(O)—O—R⁶, —N(R⁶)—C(O)—O—R⁷,—N(R⁶)—C(O)—R⁷, —N(R⁶)—C(O)—N(R⁶)(R⁷), and —C(O)—N(R⁶)(R⁷), whereinalkyl, cycloalkyl, heterocyclyl, phenyl, and phenoxy are optionallysubstituted by 1, 2, or 3 substituents selected from alkyl of 1-6 carbonatoms, cycloalkyl of 3-8 carbon atoms, alkoxy of 1-6 carbon atoms,hydroxyl, and halo; provided that R¹ is not methyl when R³ ismorpholinyl or furyl; wherein R⁶ and R⁷ are independently selected fromthe group consisting of hydrogen, alkyl of 1-6 carbon atoms, orcycloalkyl of 3-8 carbon atoms; or R⁶ and R⁷ when taken together withthe nitrogen to which they are attached form a heterocycle; R² ishydrogen, halo, cyano, alkoxy, or alkyl optionally substituted by halo;R³ is aryl, heteroaryl, or heterocyclyl, all of which are optionallysubstituted with 1, 2 or 3 substituents selected from alkyl of 1-6carbon atoms, alkoxy of 1-6 carbon atoms, cycloalkyl of 3-8 carbonatoms, cycloalkylalkyl, aryl, arylalkyl, heteroaryl, heteroarylalkyl,heterocyclyl, heterocyclylalkyl, halo, haloalkoxy, oxo, —CN, —O—R⁶,—O—C(O)—R⁶, —O—C(O)—N(R⁶)(R⁷), —S—R⁶, —N(R⁶)(R⁷), —S(═O)—R⁶, —S(═O)₂R⁶,—S(═O)₂—N(R⁶)(R⁷), —S(═O)₂—O—R⁶, —N(R⁶)—C(O)—R⁷, —N(R⁶)—C(O)—O—R⁷,—N(R⁶)—C(O)—N(R⁶)(R⁷), —C(O)—R⁶, —C(O)—O—R⁶, —C(O)—N(R⁶)(R⁷), and—N(R⁶)—S(═O)₂—R⁷, wherein the alkyl, alkoxy, cycloalkyl, aryl,heteroaryl or heterocyclyl is further optionally substituted with one ormore substituents selected from halo, hydroxyl, oxo, —CN, and —O—R⁶;with the proviso that the heteroaryl or heterocyclyl moiety includes atleast one ring nitrogen atom; X¹ is C(R⁴), X² is N or C(R⁴), and X³, X⁴,X⁵, X⁶, X⁷ and X⁸ are each C(R⁴) wherein each R⁴ is independentlyhydrogen, hydroxyl, halo, alkyl of 1-6 carbon atoms, alkoxy of 1-6carbon atoms, or cycloalkyl of 3-8 carbon atoms, wherein the alkyl orcycloalkyl is further optionally substituted with one or moresubstituents selected from halo, hydroxyl, oxo, —CF₃, —O—CF₃,—N(R⁶)(R⁷), —C(O)—R⁶, —C(O)—O—R⁷, —C(O)—N(R⁶)(R⁷), —CN, and —O—R⁶; or X⁵and X⁶ or X⁶ and X⁷ are joined to provide fused cycloalkyl, fused aryl,or fused heteroaryl, all of which are optionally substituted with alkylof 1-6 carbon atoms, hydroxyl, or halo; or a pharmaceutically acceptablesalt thereof.
 2. The compound of claim 1, wherein R¹ is optionallysubstituted alkyl, optionally substituted cycloalkyl, or optionallysubstituted heterocyclyl.
 3. The compound of claim 2, wherein alkyl,cycloalkyl, and heterocyclyl are optionally substituted by 1, 2, or 3substituents chosen from hydroxyl, halo, or cycloalkyl.
 4. The compoundof claim 3, wherein R³ is optionally substituted aryl, optionallysubstituted heteroaryl or optionally substituted heterocyclyl, whereinthe heteroaryl or heterocyclyl moieties contain 1, 2 or 3 ring nitrogenatoms.
 5. The compound of claim 4, wherein the aryl, heteroaryl, andheterocyclyl moieties are optionally substituted by alkyl, cycloalkyl,halo, cyano, or —OR⁶, in which alkyl and cycloalkyl are optionallysubstituted by hydroxyl or halo.
 6. The compound of claim 5, wherein R³is selected from

wherein: R¹¹ is hydrogen, alkyl, or cycloalkyl, wherein alkyl andcycloalkyl are optionally substituted by hydroxyl or halo; R¹² ishydrogen, alkyl, cycloalkyl, —S(═O)—R⁶ or —S(═O)₂R⁶, wherein alkyl andcycloalkyl are optionally substituted by hydroxyl or halo; and whereinthe R³ aryl, heteroaryl, and heterocyclyl moieties are optionallysubstituted by alkyl, cycloalkyl, halo, cyano, —OR⁶, in which alkyl andcycloalkyl are optionally substituted by hydroxyl or halo.
 7. A compoundselected from the group consisting of:N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(quinolin-3-yl)benzamide;N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-(6-cyclopropylpyridin-3-yl)-2,4-difluorobenzamide;4-chloro-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-(6-cyclopropylpyridin-3-yl)-2-fluorobenzamide;N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(2,2,2-trifluoro-1-methoxyethyl)-1H-imidazol-1-yl)benzamide;3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-methoxybenzamide;4-chloro-3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-(6-cyclopropylpyridin-3-yl)-2-fluorobenzamide;3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;(S)-3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-(1-phenylethyl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(1,5-naphthyridin-3-yl)benzamide;3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-isopropyl-1H-imidazol-1-yl)benzamide;3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-methylbenzamide;5-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-methylbenzamide;3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-methylbenzamide;N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(6-(2-hydroxypropan-2-yl)pyridin-3-yl)benzamide;3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-fluorobenzamide;N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4-(2,2,2-trifluoro-1-hydroxyethyl)-1H-imidazol-1-yl)benzamide;3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-methylbenzamide;N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4,5-dimethyl-1H-imidazol-1-yl)benzamide;N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-1-yl)benzamide;1-(3-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-ylcarbamoyl)phenyl)-5-methyl-1H-imidazole-4-carboxylicacid;(S)-3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-(1-phenylethyl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;(S)-3-(4,5-dimethyl-1H-imidazol-1-yl)-N-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(6-cyclopropylpyridin-3-yl)benzamide;N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-3-(pyridin-3-yl)benzamide;N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-(6-cyclopropylpyridin-3-yl)-2,4-difluorobenzamide;4-chloro-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-(6-cyclopropylpyridin-3-yl)-2-fluorobenzamide;3-(4-cyclopropyl-1H-1,2,3-triazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;(S)-5-(4-tert-butyl-1H-imidazol-1-yl)-2-fluoro-4-methyl-N-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;5-(4-tert-butyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluoro-4-methylbenzamide;(S)-5-(4-cyclopropyl-1H-imidazol-1-yl)-2,3-difluoro-N-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;5-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2,3-difluorobenzamide;4-chloro-5-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluorobenzamide;(S)-4-chloro-5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-N-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;5-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2,4-difluorobenzamide;(S)-3-(4-cyclopropyl-1H-imidazol-1-yl)-4-fluoro-N-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-fluorobenzamide;5-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluoro-4-methylbenzamide;(S)-5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methyl-N-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;5-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluorobenzamide;and(S)-3-(4-cyclopropyl-1H-imidazol-1-yl)-4-methyl-N-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;or a pharmaceutically acceptable salt thereof.
 8. A compound selectedfrom the group consisting of:(S)-3-(4,5-dimethyl-1H-imidazol-1-yl)-N-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;3-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;5-(4-tert-butyl-1H-imidazol-1-yl)-4-chloro-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluorobenzamide;(S)-5-(4-tert-butyl-1H-imidazol-1-yl)-4-chloro-2-fluoro-N-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluoro-5-(4-(1-hydroxy-2-methylpropan-2-yl)-1H-imidazol-1-yl)-4-methylbenzamide;N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluoro-4-methyl-5-(4-(1-methylcyclopropyl)-1H-imidazol-1-yl)benzamide;(S)-2-fluoro-4-methyl-5-(4-(1-methylcyclopropyl)-1H-imidazol-1-yl)-N-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-methylbenzamide;5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methyl-N-(6-(4-(1-methylcyclopropyl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;5-(4-cyclobutyl-1H-imidazol-1-yl)-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluoro-4-methylbenzamide;(S)-5-(4-cyclobutyl-1,4-imidazol-1-yl)-2-fluoro-4-methyl-N-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;N-(6-(4-cyclobutyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methylbenzamide;N-(6-(4-cyclopentyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methylbenzamide;N-(6-(4-cyclohexyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methylbenzamide;5-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-(cyclopropylmethyl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluoro-4-methylbenzamide;(S)-5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-N-(6-(4-(1-methoxypropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-methylbenzamide;N-(6-(4-tert-butyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methylbenzamide;5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methyl-N-(6-(4-(tetrahydro-2H-pyran-4-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methyl-N-(6-(4-(oxetan-3-ylmethyl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;N-(6-(4-(azetidin-3-ylmethyl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methylbenzamide;5-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-(2-(dimethylamino)ethyl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluoro-4-methylbenzamide;5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-N-(6-(4-(2-methoxyethyl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-methylbenzamide;5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methyl-N-(6-(4-(2,2,2-trifluoroethyl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;5-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-(2,2-difluoroethyl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluoro-4-methylbenzamide;5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methyl-N-(6-(4-(tetrahydrofuran-3-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;(S)-5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methyl-N-(6-(4-(pyrrolidin-3-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluoro-5-(4-isopropyl-1H-imidazol-1-yl)-4-methylbenzamide;(S)-2-fluoro-5-(4-isopropyl-1H-imidazol-1-yl)-4-methyl-N-(6-(4-(1,1,1-trifluoropropan-2-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;2-fluoro-5-(4-isopropyl-1H-imidazol-1-yl)-N-(6-(4-isopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-4-methylbenzamide;5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methyl-N-(6-(4-(1-(2,2,2-trifluoroethyl)azetidin-3-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;5-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-(1-(2,2-difluoroethyl)azetidin-3-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluoro-4-methylbenzamide;N-(6-(4-(1-acetylazetidin-3-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methylbenzamide;5-(4-cyclopropyl-1H-imidazol-1-yl)-N-(6-(4-(3,3-difluorocyclobutyl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2-fluoro-4-methylbenzamide;5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methyl-N-(6-(4-(3-methyloxetan-3-yl)-4H-1,2,4-triazol-3-yl)pyridin-2-yl)benzamide;and5-(4-cyclopropyl-1H-imidazol-1-yl)-2-fluoro-4-methyl-N-(6-(4-(1-methylpiperidin-4-yl)-4H-1,2,4-triazol-3-yl)pyridin-2yl)benzamide;or a pharmaceutically acceptable salt thereof.
 9. A compound selectedfrom the group consisting of:N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-3,3′-bipyridine-5-carboxamide;N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-5-phenylnicotinamide;N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-2-phenylisonicotinamide;6′-cyclopropyl-N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-2,3′-bipyridine-4-carboxamide;5-(2,5-difluorophenyl)-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)nicotinamide;N-(3-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)phenyl)-6-(6-cyclopropylpyridin-3-yl)pyrimidine-4-carboxamide;6′-cyclopropyl-N-(6-(4-cyclopropyl-4H-1,2,4-triazol-3-yl)pyridin-2-yl)-2,3′-bipyridine-4-carboxamide;and2-hydroxy-N-(3-(4-methyl-4H-1,2,4-triazol-3-yl)phenyl)-6-phenylpyrimidine-4-carboxamide;or a pharmaceutically acceptable salt thereof.
 10. A pharmaceuticalcomposition comprising one or more compounds according to claim 1 and apharmaceutically acceptable carrier.